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Sample records for adjuvant photodynamic therapy

  1. Adjuvant photodynamic therapy in surgical management of cerebral tumors

    NASA Astrophysics Data System (ADS)

    Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

    1993-03-01

    We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

  2. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  3. First experimental experience in adjuvant intraoperative photodynamic therapy (AIOPDT) in S117 sarcoma in mice

    NASA Astrophysics Data System (ADS)

    Winkler, Steffi; Prosst, Ruediger L.; Haase, Thomas; Flechtenmacher, Chr.; Stern, J.; Gahlen, Johannes

    2001-10-01

    The effectiveness of photodynamic therapy (PDT) as an adjuvant treatment for diverse malignant tumors has been investigated in numerous studies. The therapeutic success and extent of side effects of PDT is mainly determined by the applied photosensitizer (PS) and laser energy. Adjuvant intraoperative photodynamic therapy (AIOPDT) using the PS mTHPC (meso-Tetrahydroxyphenylchlorin) causes selective tumor cell death when combined with laser irradiation of a PS specific wavelength (652 nm). Our study proved AIOPDT as an efficient modality to significantly increase postoperative recurrence-free survival after R1/R2 resection of a subcutaneously implanted soft tissue sarcoma in mice. We used mTHPC in a dose of (0,3 mg/kg BW) and a laser light energy of 5 Joule (irradiation time: 50 seconds). First results showed an increase of postoperative recurrence-free survival (Median: 103 days) in 5 animals treated with AIOPDT compared to a control group of 7 animals (Median: 20 days). The tissue specific accumulation of mTHPC was determined by point spectrofluorometry and showed a 2.28 higher PS-accumulation in the tumor center, tumor bed (1.5) and overlying skin (3.8) compared to muscle tissue (1.0) as reference parameter. Our first experimental data recommend AIOPDT to be an efficient adjuvant method to prolonge recurrence-free survival after tumor resection.

  4. Evaluation of monophosphoryl lipid A as an immune adjuvant for photodynamic therapy in a rat sarcoma model: preliminary results

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Griffey, Stephen M.; Madewell, Bruce R.

    1999-06-01

    Photodynamic therapy (PDT) is a treatment option for several forms of human cancer, and like traditional chemotherapy and ionizing radiation therapy, PDT alone is not curative for some cases. Recent efforts have aimed at developing strategies for adjuvant therapy for PDT. Given the nature of PDT-mediated cell damage, immunotherapy is a promising adjuvant for long-term control of solid tumors. A candidate immune stimulant for use with PDT is monophosphoryl lipid A (MLA), a non-toxic fraction of the endotoxin molecule. The hypothesis is that adjuvant MLA immunotherapy with PDT will improve local tumor control and prevent growth of subsequently implanted tumor cells when compared to PDT alone. To date, no significant differences in circulating leukocyte populations or tumor infiltrating lymphocyte populations have been identified in 9L tumor-bearing F344 rats after systemic administrations of MLA. Likewise, no significant difference has been identified in local tumor control following PDT of 9L tumors with or without adjuvant MLA. Further results are pending.

  5. Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

    NASA Astrophysics Data System (ADS)

    Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

    2014-02-01

    Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ?T up to 80°C was measured.

  6. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  7. Photodynamic therapy with fullerenes†

    PubMed Central

    Mroz, Pawel; Tegos, George P.; Gali, Hariprasad; Wharton, Tim; Sarna, Tadeusz; Hamblin, Michael R.

    2010-01-01

    Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended ?-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases. PMID:17973044

  8. Melanoma adjuvant therapy.

    PubMed

    Tarhini, Ahmad A; Thalanayar, Prashanth M

    2014-06-01

    Adjuvant therapy targets melanoma micrometastases in patients with surgically resected disease that carry a high risk of death from melanoma recurrence. In this setting, adjuvant therapy provides the greatest opportunity for cure before progression into advanced inoperable stages. In randomized clinical trials, interferon-alfa has been shown to have a significant impact on relapse-free survival and, at high dosage, on overall survival compared with observation (E1684) and the GMK vaccine (E1694). This article reviews melanoma adjuvant therapy along with the ongoing and planned clinical trials. PMID:24880942

  9. Adjuvant Therapy of Melanoma.

    PubMed

    Davar, Diwakar; Kirkwood, John M

    2016-01-01

    The incidence of melanoma is rapidly increasing, especially in younger female and older male patients. Recent fundamental advances in our knowledge of melanoma tumorigenesis have established roles for inhibitors of the MAPK pathway and regulatory immune checkpoints CTLA-4 and PD-1/PD-L1. However, the majority of patients continue to present with non-metastatic disease-typically managed with surgical resection and adjuvant therapy. High-dose IFN-?2b (HDI) is the main adjuvant therapeutic mainstay in high-risk disease following definitive resection. In this chapter, we review the evidence supporting the use of adjuvant HDI in high-risk melanoma. We also discuss some of the other treatment modalities that have been evaluated including vaccines, chemotherapy, and radiotherapy. PMID:26601863

  10. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-?2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-?2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  11. Photodynamic therapy for epilepsy

    NASA Astrophysics Data System (ADS)

    Zusman, Edie; Sidhu, Manpreet; Coon, Valerie; Scott, Nicholas; Bisland, Stuart; Tsukamoto, Tara

    2006-02-01

    Epilepsy is surgically curable if the seizure focus can be localized and does not include areas of eloquent cortex. Because epileptic cells are indistinct from surrounding brain, resection typically includes normal tissue. Using the rat kindling model of epilepsy, we evaluated Photodynamic Therapy (PDT) as a super-selective lesioning technique. We present a series of pilot studies to evaluate: 1) Protoporphyrin IX (PpIX) fluorescence, 2) the efficacy of PDT to raise seizure thresholds, 3) the safety of PDT using behavioral studies, and 4) histologic results. Bipolar electrodes were chronically implanted into the cortex and animals received successive low-level stimulation generating seizures of increasing severity. Following 5-aminolevulinic acid (ALA) administration, fully kindled rats received electrical stimulation to induce a generalized seizure. Animals were irradiated with laser light focused onto a temporal craniectomy. Our results show: 1) an increase in PpIX fluorescence in the seizure group, 2) PDT treated animals failed to demonstrate seizure activity following repeat stimulation, 3) no statistically significant difference between treated and control animals were observed on behavioral tests, 4) histology showed pyknotic hippocampal pyramidal cells in the CA3 region without areas of obvious necrosis. In conclusion, this is the first report of heightened PpIX-mediated fluorescence in epileptic brain. The selective accumulation of PpIX with laser PDT may provide a less invasive and more precise technique for obliteration of epileptic foci. PDT warrants additional research to determine if this technique may augment or replace existing procedures for the surgical management of epilepsy.

  12. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-?2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-?2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  13. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma. PMID:26550910

  14. Photosensitizers and Photodynamic Therapy: Verteporfin.

    PubMed

    Battaglia Parodi, Maurizio; La Spina, Carlo; Berchicci, Luigi; Petruzzi, Giuseppe; Bandello, Francesco

    2016-01-01

    Photodynamic therapy (PDT) is a phototherapy in which a photosensitive dye is injected into a peripheral vein and activated by light in order to occlude choroidal vessels or change their permeability. PDT has been largely applied in the treatment of choroidal neovascularization (CNV), especially CNV related to age-related macular degeneration, but was also of benefit in other diseases, including central serous chorioretinopathy and choroidal hemangioma. PMID:26501167

  15. More Adventures in Photodynamic Therapy

    PubMed Central

    Kessel, David

    2015-01-01

    Photodynamic therapy is a procedure that can provide a selective eradication of neoplastic disease if sufficient drug, light, and oxygen are available. As this description suggests, it involves the photosensitization of malignant tissues to irradiation with photons in the visible range. While not suitable for tumors at unknown loci, it can be of use for eradication of cancer at surgical margins and therapy at sites where substantial surgery might otherwise be involved. Drug development has been delayed by several factors including the reluctance of major pharmaceutical firms in the United States to invest in this technology along with some unwise approaches in the past. PMID:26151850

  16. Treatment of rheumatoid arthritis using photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

    1995-03-01

    The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

  17. Phthalocyanine photodynamic therapy of experimental iris neovascularization.

    PubMed

    Miller, J W; Stinson, W G; Gregory, W A; el-Koumy, H A; Puliafito, C A

    1991-11-01

    Photodynamic therapy using chloroaluminum sulfonated phthalocyanine (CASPc) effectively closed experimental iris neovascularization induced in 6 eyes of cynomolgus monkeys by argon laser retinal vein occlusion. Neovascularization was followed by iris photography, fluorescein angiography, and histopathologic examination by light and electron microscopy. Intravenous injection of CASPc followed by irradiation with 675 nm light damaged endothelial cells and pericytes, leading to exposure of the basal lamina and thrombotic occlusion of the blood vessels. Surrounding tissue appeared preserved without evidence of thermal damage. Resorption of occluded vessels by macrophages began 2 to 3 days after photodynamic therapy. Neovascularization reappeared 7 days after photodynamic therapy, probably representing growth of new vessels. Photodynamic therapy with CASPc may be a useful adjunct in the treatment of iris neovascularization. The model is useful in elucidating the ultrastructural changes observed after photodynamic therapy using phthalocyanines. PMID:1724793

  18. Augmentation of tumor immunity with ENHANZYN adjuvant following verteporfin PDT: photodynamic vaccination (PDV)

    NASA Astrophysics Data System (ADS)

    Curry, P. M.; Stewart, A. J.; Hardwicke, L.; Smits, Claire; North, John R.

    2001-07-01

    The immune system is implicated in the mechanism of tumor destruction following photodynamic therapy (PDT). Several investigators have shown that immune stimulation can augment PDT. In this study, a single intratumoral injection of ENHANZYNTM adjuvant was administered to tumor-bearing mice immediately following verteporfin PDT in a therapeutic modality referred to as Photodynamic Vaccination (PDV). After optimal PDT, little difference in the rate of tumor re-growth or time to tumor reappearance was seen upon addition of the adjuvant. This may be as expected as this treatment regimen results in effective long-term tumor cure in mice. The effect of adjuvant and sub-optimal PDT was less clear as both groups treated with either a high or low does of adjuvant showed tumor re-growth earlier than those animals treated with PDT alone. However, tumors of mice receiving sub-optimal PDT followed by high dose immune adjuvant did not show the rapid, uncontrolled growth seen in other groups and, in the majority of cases, tumor volume decreased steadily with time. This resulted in a superior period of survival despite the animals being tumor-bearing. Interestingly, the data obtained in this study clearly demonstrates the ability of PDT to protect against re- challenge with a second round of tumor implantation. This was seen in all groups and stresses the importance of the immune response in PDT tumor control. Addition of the high immune adjuvant does to sub-optimal PDT appeared to be the most effective treatment group in this respect, giving complete protection against tumor re-implantation.

  19. Photodynamic therapy of acne vulgaris.

    NASA Astrophysics Data System (ADS)

    Ershova, Ekaterina Y.; Karimova, Lubov N.; Kharnas, Sergey S.; Kuzmin, Sergey G.; Loschenov, Victor B.

    2003-06-01

    Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) was tested for the treatment of acne vulgaris. Patients with acne were treated with ALA plus red light. Ten percent water solution of ALA was applied with 1,5-2 h occlusion and then 18-45 J/cm2 630 nm light was given. Bacterial endogenous porphyrins fluorescence also was used for acne therapy. Treatment control and diagnostics was realized by fluorescence spectra and fluorescence image. Light sources and diagnostic systems were used: semiconductor laser (?=630 nm, Pmax=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (?=635 nm, P=2W, p=50 mW/cm2), (UFPh-630-01-BIOSPEC); high sensitivity CCD video camera with narrow-band wavelength filter (central wavelength 630 nm); laser electronic spectrum analyzer for fluorescent diagnostics and photodynamic therapy monitoring (LESA-01-BIOSPEC). Protoporphyrin IX (PP IX) and endogenous porphyrins concentrations were measured by fluorescence at wavelength, correspondingly, 700 nm and 650 nm. It was shown that topical ALA is converted into PP IX in hair follicles, sebaceous glands and acne scars. The amount of resulting PP IX is sufficient for effective PDT. There was good clinical response and considerable clearance of acne lesion. ALA-PDT also had good cosmetic effect in treatment acne scars. PDT with ALA and red light assist in opening corked pores, destroying Propionibacterium acnes and decreasing sebum secretion. PDT treatment associated with several adverse effects: oedema and/or erytema for 3-5 days after PDT, epidermal exfoliation from 5th to 10th day and slight pigmentation during 1 month after PDT. ALA-PDT is effective for acne and can be used despite several side effects.

  20. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.

  1. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

    Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

    1993-05-01

    Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

  2. Photodynamic Therapy, Optical Trapping and Photostimulated Emission Using

    E-print Network

    Van Stryland, Eric

    , which are generally near infrared (NIR) light, into a higher energy outcome photon (e.g., NIR, visiblePhotodynamic Therapy, Optical Trapping and Photostimulated Emission Using Upconverting nanothermometry MRI Photodynamic Therapy #12;· Attractive features: - Stability with respect to photobleaching

  3. Functionalized Fullerenes in Photodynamic Therapy

    PubMed Central

    Huang, Ying-Ying; Sharma, Sulbha K.; Yin, Rui; Agrawal, Tanupriya; Chiang, Long Y.; Hamblin, Michael R.

    2014-01-01

    Since the discovery of C60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C60, C70 and C84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT. PMID:25544837

  4. Inorganic Nanoparticles for Photodynamic Therapy.

    PubMed

    Colombeau, L; Acherar, S; Baros, F; Arnoux, P; Gazzali, A Mohd; Zaghdoudi, K; Toussaint, M; Vanderesse, R; Frochot, C

    2016-01-01

    Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters. PMID:26589507

  5. Can nanotechnology potentiate photodynamic therapy?

    PubMed Central

    Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Chiang, Long Y.

    2015-01-01

    Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nano-technology potentiate PDT?” PMID:26361572

  6. Functionalized fullerenes in photodynamic therapy.

    PubMed

    Huang, Ying-Ying; Sharma, Sulbha K; Yin, Rui; Agrawal, Tanupriya; Chiang, Long Y; Hamblin, Michael R

    2014-09-01

    Since the discovery of C60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine CO60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C60, C70 and C84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT. PMID:25544837

  7. Adjuvant therapy in pancreatic cancer

    PubMed Central

    Ghaneh, Paula; Slavin, John; Sutton, Robert; Hartley, Mark; Neoptolemos, John P

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients. PMID:11819814

  8. Porphyrins for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Pascu, Mihail-Lucian

    2001-06-01

    Photodynamic therapy (PDT) of cancer is based on the dye- sensitized photooxidation of different biological targets in the tumoral tissue yielding to a photochemically induced cell's death. The effectiveness of this treatment method depends on the photophysical and photochemical properties of the used photosensitizer-drug during the irradiation with visible light (laser beam) and/or the ionizing radiation. The purpose of this paper is to summarize the photodynamic therapy applications: substitution effects, ionization and aggregation processes effects, photodegradation reaction implications, the correlation with some medical applications on human brain cells.

  9. Laser-mediated photodynamic therapy.

    PubMed

    Alexiades-Armenakas, Macrene

    2006-01-01

    Photodynamic therapy (PDT) has evolved since its inception at the beginning of the 20th century, when it was defined as an oxygen-dependent reaction between a photosensitizing dye and light. Photosensitizers and light sources have since been continually optimized for distinct applications and tissues. Systemic porphyrins, such as hematoporphyrin, were the first photosensitizers to be used, mostly to treat tumors. The first light sources used were broad-band, noncoherent lights, such as quartz, xenon, tungsten, or halogen lamps. The wavelengths of light chosen were based upon the absorption spectrum of porphyrins: blue because the largest peak is at 400 nm (the Soret band) and red because of its greater penetration depth but lesser absorption at 650 nm (a Q band). Systemic photosensitizers caused prolonged photosensitivity, and broad-band light sources had limitations and side effects. The development of topical photosensitizers, such as 5-aminolevulinic acid, and the advent of lasers in recent years have advanced PDT for cutaneous use. In the 1990s, red lasers were applied to PDT because of their increased skin penetration despite lesser absorption by porphyrins. Broad-band blue light and red light have been studied extensively, the former achieving Food and Drug Administration approval in combination with topical aminolevulinic acid for the treatment of actinic keratosis in 1997. These lasers and light sources caused significant side effects, such as discomfort, erythema, crusting, blistering, and dyspigmentation. The recent application of the long-pulsed pulsed dye laser (595 nm) after topical aminolevulinic acid greatly minimized side effects without compromising efficacy. Long-pulsed pulsed dye laser-mediated PDT has since been shown to be effective in treatment of actinic keratosis, actinic cheilitis, sebaceous hyperplasia, lichen sclerosus, and, most recently, acne vulgaris. Finally, intense pulsed light sources have been introduced to PDT for the treatment of photodamage and acne, offering advantages of versatility in wavelengths and applications. PMID:16427502

  10. Photodynamic therapy of diseased bone

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.

  11. Antimicrobial Photodynamic Inactivation and Photodynamic Therapy for Infections

    PubMed Central

    Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) was initially discovered over 100 years ago by its ability to kill microorganisms, but its use to treat infections clinically has not been much developed. However, the present relentless increase in antibiotic resistance worldwide and the emergence of strains that are resistant to all known antibiotics has stimulated research into novel antimicrobial strategies such as PDT that are thought to be unlikely to lead to the development of resistance. In this chapter we will cover the use of PDT to kill pathogenic microbial cells in vitro and describe a mouse model of localized infection and its treatment by PDT without causing excessive damage to the host tissue. PMID:20552347

  12. Retinoblastoma: might photodynamic therapy be an option?

    PubMed

    Teixo, Ricardo; Laranjo, Mafalda; Abrantes, Ana Margarida; Brites, Gonçalo; Serra, Arménio; Proença, Rui; Botelho, Maria Filomena

    2015-12-01

    Retinoblastoma is a tumor that mainly affects children under 5 years, all over the world. The origin of these tumors is related with mutations in the RB1 gene, which may result from genetic alterations in cells of the germ line or in retinal somatic cells. In developing countries, the number of retinoblastoma-related deaths is higher due to less access to treatment, unlike what happens in developed countries where survival rates are higher. However, treatments such as chemotherapy and radiotherapy, although quite effective in treating this type of cancer, do not avoid high indices of mortality due to secondary malignances which are quite frequent in these patients. Additionally, treatments such as cryotherapy, thermotherapy, thermochemotherapy, or brachytherapy represent other options for retinoblastoma. When all these approaches fail, enucleation is the last option. Photodynamic therapy might be considered as an alternative, particularly because of its non-mutagenic character. Photodynamic therapy is a treatment modality based on the administration of photosensitizing molecules that only upon irradiation of the tumor with a light source of appropriate wavelength are activated, triggering its antitumor action. This activity may be not only due to direct damage to tumor cells but also due to damage caused to the blood vessels responsible for the vascular supply of the tumor. Over the past decades, several in vitro and in vivo studies were conducted to assess the effectiveness of photodynamic therapy in the treatment of retinoblastoma, and very promising results were achieved. PMID:25579236

  13. Multiphoton Biomedical Imaging and Photodynamic Therapy: Agents & Applications

    E-print Network

    Van Stryland, Eric

    -reactive model Hydrophobic and hydrophilic dyes Two-Photon Photodynamic Therapy #12;"Two-photon laser scanning at the focus of the scanning pulsed-infrared laser beam, resulting in a much less harmful light dose duringMultiphoton Biomedical Imaging and Photodynamic Therapy: Agents & Applications Kevin D. Belfield

  14. Photodynamic therapy: a review of applications in neurooncology and neuropathology

    NASA Astrophysics Data System (ADS)

    Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

    2015-06-01

    Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

  15. Cell Death Pathways in Photodynamic Therapy of Cancer

    E-print Network

    Mroz, Pawel

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be ...

  16. Photodynamic therapy for treatment subretinal neovascularization

    NASA Astrophysics Data System (ADS)

    Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

  17. Acceleration Of Wound Healing Ny Photodynamic Therapy

    SciTech Connect

    Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

    2000-08-22

    Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

  18. Photodynamic therapy of early esophageal cancer.

    PubMed

    Filonenko, Elena V; Sokolov, Victor V; Chissov, Valery I; Lukyanets, Evgeny A; Vorozhtsov, Georgy N

    2008-09-01

    In 1992-2006 at P.A. Hertsen Moscow Oncology Research Institute photodynamic therapy (PDT) was performed in 48 esophageal cancer patients (total 48 lesions). For PDT we used Russian photosensitizers (Photogem, Photosens, Radachlorin, Alasens), Russian diode lasers (Crystall) and endoscopic equipment. As a result of PDT complete regression was in 77% of esophageal cancer lesions, partial regression was in 23%. The follow-up period was 3-11 years. Median of survival was in 4.59 years of esophageal cancer patient. PMID:19356654

  19. Hormonal component of tumor photodynamic therapy response

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

  20. Singlet oxygen dosimetry modeling for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Liang, Xing; Wang, Ken Kang-hsin; Zhu, Timothy C.

    2012-02-01

    Photodynamic therapy (PDT) is an important treatment modality for cancer and other localized diseases. In addition to PDT dose, singlet oxygen (1O2) concentration is used as an explicit PDT dosimetry quantity, because 1O2 is the major cytotoxic agent in photodynamic therapy, and the reaction between 1O2 and tumor tissues/cells determines the treatment efficacy. 1O2 concentration can be obtained by the PDT model, which includes diffusion equation for the light transport in tissue and macroscopic kinetic equations for the generation of the singlet oxygen. This model was implemented using finite-element method (FEM) by COMSOL. In the kinetic equations, 5 photo-physiological parameters were determined explicitly to predict the generation of 1O2. The singlet oxygen concentration profile was calculated iteratively by comparing the model with the measurements based on mice experiments, to obtain the apparent reacted 1O2concentration as an explicit PDT dosimetry quantity. Two photosensitizers including Photofrin and BPD Verteporfin, were tested using this model to determine their photo-physiological parameters and the reacted 1O2 concentrations.

  1. Drug Carrier for Photodynamic Cancer Therapy

    PubMed Central

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  2. Scope of photodynamic therapy in periodontics.

    PubMed

    Kumar, Vivek; Sinha, Jolly; Verma, Neelu; Nayan, Kamal; Saimbi, C S; Tripathi, Amitandra K

    2015-01-01

    Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer) activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis. PMID:26481895

  3. Photonic metallic nanostructures in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Fierascu, R. C.; Dumitriu, Irina

    2009-01-01

    Plasmons are resonant modes that involve the interaction between free charges and light. Nanoparticle-based photonic explorers have been developed for photodynamic therapy (PDT). PDT has been widely used in both oncological (e.g., tumors) and nononcological (e.g., age-related macular degeneration, localized infection, and nonmalignant skin conditions) applications. Three primary components are involved in PDT: light, a photosensitizing drug, and oxygen. The photosensitizer adsorbs light energy, which it then transfers to molecular oxygen to create an activated form of oxygen called singlet oxygen. The singlet oxygen is a cytotoxic agent and reacts rapidly with cellular components to cause damage that ultimately leads to cell death and tumor destruction. The changed topography of the film surface after deposition is caused by a local material transport and a material separation between formed particles (probably AgNO3) and an embedding polymer matrix as chitosan. This paper focuses on the current use of injectable in situ Au/(Ag)/chitosan hydrogels in cancer photodynamic treatment. Formulation protocols for their cytotoxic properties, their effect on cell growth in vitro and inhibition of tumor growth in vivo using mouse models, are discussed.

  4. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    E-print Network

    Mroz, Pawel

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis ...

  5. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    PubMed Central

    Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

    2011-01-01

    Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

  6. Feasibility of chemiluminescence as photodynamic therapy dosimetor

    NASA Astrophysics Data System (ADS)

    Qin, Yanfang; Xing, Da; Zhong, Xueyun; Zhou, Jin; Luo, Shiming; Chen, Qun

    2006-09-01

    Photodynamic therapy (PDT) utilizes light energy of a proper wavelength to activate a pre-administered photosensitizer in a target tissue to achieve a localized treatment effect. Current treatment protocol of photodynamic therapy (PDT) is defined by empirical values such as irradiation light fluence, fluence rate and the amount of administered photosensitizer. It is well known that Singlet oxygen is the most important cytotoxic agent responsible for PDT biological effects. An in situ monitoring of singlet oxygen production during PDT would provide a more accurate dosimeter for PDT. The presented study has investigated the feasibility of using Fhioresceinyl Cypridina Luciferin Analog (FCLA), a singlet oxygen specific chemiluminescence (CL) probe, as a dosimetric tool for PDT. Raji lymphoma cell suspensions were sensitized with Photofrin (R) of various concentrations and irradiated with 635 nm laser light at different fluence rates. FCLA-CL from singlet oxygen produced by the treatment was measured, in real time, with a photon multiplier tube (PMT) system, and linked to the cytotoxicity resulting from the treatment. We have observed that the CL intensity of FCLA is dependent on the PDT treatment parameters. After each PDT treatment and CL measurement, the irradiated cells were evaluated by MIT assay for their Viability. The results show that the cell viability is highly related to the accumulated CL. With 10 II quencher, we confirmed that the CL was mainly related to PDT produced 10 II The results suggest that the FCLA-CL system can be an effective means in measuring PDT 1O II production and may provide an alternative dosimetry technique for PDT.

  7. Photodynamic Therapy for Infections: Clinical Applications

    PubMed Central

    Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.

    2012-01-01

    Background and Objective Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. Study Design/Materials and Methods The published peer-reviewed literature was reviewed between 1960 and 2011. Results The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. Conclusion As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. PMID:22057503

  8. Combination immunotherapy and photodynamic therapy for cancer

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.; Castano, Ana P.; Mroz, Pawel

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  9. Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX

    E-print Network

    Gao, Jinming

    , which are hydrophobic and have intrin- sically low water solubilities. Excipient molecules such as lipid 10 January 2011 Keywords: Polymeric micelles Photodynamic therapy Protoporphyrin IX Singlet oxygen the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT

  10. Photodynamic Therapy for Obstructive Esophageal Malignancies

    PubMed Central

    McCaughan, James S.

    1999-01-01

    Objectives Determine factors affecting survival rates, benefits and complications of patients with obstructive esophageal cancer treated with photodynamic therapy (PDT). Methods From 1982 to January 1998, we used PDT to treat 140 patients with obstructive adeno or squamous carcinoma and evaluated survival up to November 1998. All patients had failed, refused, or were ineligible for surgery, ionizing radiation or chemotherapy. The effect of different variables on survival was estimated using multivariate analysis. The Karnofsky Performance Status (KPS), weight, diet and complications were recorded and biopsies and brushings were taken at each endoscopy. At the beginning and end of each endoscopy the minimal diameter open of the esophagus, and the length, thickness and color of the tumor were recorded. Edema, exudate, bleeding, and mucositis were evaluated and recorded on an ordinal scale. Results The only significant variable affecting survival was the clinical stage. The median survival after PDT for all patients was 6.5 months (mean = 13.9). Kaplan–Meier survival after PDT curves were statistically significantly different when stratified by the clinical Stage at the time of PDT (p < 0.0001). Median survival (months) were for: Stage I = 56; Stage II = 12; Stage III = 6.5; Stage IV = 3.5. Analysis of each individual stage showed the KPS was the only confounding variable with a statistically significant effect on survival after PDT and this was only for Stages III and IV. The most significant effect occurred when the KPS was ? 70. For Stage III the median survival when the KPS was ? 70 was 7.7 months and for a KPS < 70 it was 5.0 months (p = 0.0001). For Stage IV the median survival when the KPS was ? 70 was 5.5 months and for a KPS < 70 it was 2.5 months (p = 0.0002). The mean minimum diameter open before PDT was 6.2 mm (median 6.0mm) and at the end of the PDT treatment endoscopy 11.1 mm (median 12.0 mm) for a mean increase in the minimum diameter open of 4.9 mm (median 5.0 mm) This was statistically significant using paired t-tests (p < 0.0001). Conclusions Photodynamic therapy for esophageal carcinoma caused minimal complications and procedure related mortality. Complete obstruction can be relieved by the end of the PDT endoscopy. The length of palliation for “non-curative” patients was equal to or better than that reported historically for most other treatment regimens. PMID:18493499

  11. Photodynamic therapy (PDT) as a biological modifier

    NASA Astrophysics Data System (ADS)

    Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.

    1996-04-01

    The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).

  12. Integrating spheres for improved skin photodynamic therapy.

    PubMed

    Glennie, Diana L; Farrell, Thomas J; Hayward, Joseph E; Patterson, Michael S

    2010-01-01

    The prescribed radiant exposures for photodynamic therapy (PDT) of superficial skin cancers are chosen empirically to maximize the success of the treatment while minimizing adverse reactions for the majority of patients. They do not take into account the wide range of tissue optical properties for human skin, contributing to relatively low treatment success rates. Additionally, treatment times can be unnecessarily long for large treatment areas if the laser power is not sufficient. Both of these concerns can be addressed by the incorporation of an integrating sphere into the irradiation apparatus. The light fluence rate can be increased by as much as 100%, depending on the tissue optical properties. This improvement can be determined in advance of treatment by measuring the reflectance from the tissue through a side port on the integrating sphere, allowing for patient-specific treatment times. The sphere is also effective at improving beam flatness, and reducing the penumbra, creating a more uniform light field. The side port reflectance measurements are also related to the tissue transport albedo, enabling an approximation of the penetration depth, which is useful for real-time light dosimetry. PMID:21054127

  13. Photodynamic therapy in dermatology--an update.

    PubMed

    Babilas, Philipp; Karrer, Sigrid; Sidoroff, Alexis; Landthaler, Michael; Szeimies, Rolf-Markus

    2005-06-01

    Topical photodynamic therapy (PDT) is a well-established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5-aminolevulinic acid (5-ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light-emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment. PMID:15888131

  14. The use of photodynamic therapy in dermatology.

    PubMed

    Babilas, P; Szeimies, R M

    2010-10-01

    In dermatology, topical photodynamic therapy (PDT) is a well established treatment modality which has mainly shown to be effective for dermato-oncologic conditions like actinic keratosis, Bowen's disease, in-situ squamous cell carcinoma and superficial basal cell carcinoma. However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare as well as for aesthetic indications like photo aged skin or sebaceous gland hyperplasia. Recent work has been focused on the development and evaluation of topical photosensitizers like the hem precursor 5-aminolevulinic acid or its methyl ester inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or LED arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness < 2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment. PMID:20930696

  15. Pecularities of clinical photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Litvin, Grigory D.; Astrakhankina, Tamara A.

    1996-01-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder rectum and other locations has been made. During 1992 - 1995 478 tumoral foci in 125 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of severe accompanying diseases or because of old age. A part of the patients had PDT because of recurrences or intradermal metastases in 1 - 2 years after surgical, radial or combined treatment. Two home-made preparations were used as photosensitizers: Photohem (hematoporphyrine derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were: the argon pumped dye laser (`Innova-200', `Coherent') and home-made laser devices: copper-vapor laser-pumped dye laser (`Yakhroma-2', Frjazino), gas-discharge unit `Ksenon' (wavelength 630 nm), gold-vapor laser (wavelength 627.8 nm) for Photohem; while for Photosense sessions we used solid-state laser on ittrium aluminate `Poljus-1' (wavelength 670 nm). Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 92% of patients including complete regression of tumors in 66.4% and partial in 25.6%. Currently, this new perspective technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

  16. Polymeric Nanoparticles for Cancer Photodynamic Therapy.

    PubMed

    Conte, Claudia; Maiolino, Sara; Pellosi, Diogo Silva; Miro, Agnese; Ungaro, Francesca; Quaglia, Fabiana

    2016-01-01

    In chemotherapy a fine balance between therapeutic and toxic effects needs to be found for each patient, adapting standard combination protocols each time. Nanotherapeutics has been introduced into clinical practice for treating tumors with the aim of improving the therapeutic outcome of conventional therapies and of alleviating their toxicity and overcoming multidrug resistance.Photodynamic therapy (PDT) is a clinically approved, minimally invasive procedure emerging in cancer treatment. It involves the administration of a photosensitizer (PS) which, under light irradiation and in the presence of molecular oxygen, produces cytotoxic species. Unfortunately, most PSs lack specificity for tumor cells and are poorly soluble in aqueous media, where they can form aggregates with low photoactivity. Nanotechnological approaches in PDT (nanoPDT) can offer a valid option to deliver PSs in the body and to solve at least some of these issues. Currently, polymeric nanoparticles (NPs) are emerging as nanoPDT system because their features (size, surface properties, and release rate) can be readily manipulated by selecting appropriate materials in a vast range of possible candidates commercially available and by synthesizing novel tailor-made materials. Delivery of PSs through NPs offers a great opportunity to overcome PDT drawbacks based on the concept that a nanocarrier can drive therapeutic concentrations of PS to the tumor cells without generating any harmful effect in non-target tissues. Furthermore, carriers for nanoPDT can surmount solubility issues and the tendency of PS to aggregate, which can severely affect photophysical, chemical, and biological properties. Finally, multimodal NPs carrying different drugs/bioactive species with complementary mechanisms of cancer cell killing and incorporating an imaging agent can be developed.In the following, we describe the principles of PDT use in cancer and the pillars of rational design of nanoPDT carriers dictated by tumor and PS features. Then we illustrate the main nanoPDT systems demonstrating potential in preclinical models together with emerging concepts for their advanced design. PMID:26589506

  17. Laser effect in photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Brezoi, Dragos-Viorel; Neagu, Monica; Manda, Gina; Constantin, Carolina

    2007-03-01

    Photodynamic therapy is a method that provides a reasonable alternative to other treatment modalities for patients with certain cancers, and in some cases may be the preferred treatment. The therapy implies the intravenous administration of a light-sensitive substance, the photosensitizer. The used sensitizer must absorb at long wavelength. For these purposes, the carbon dioxide laser, He-Ne and the argon laser are particularly suitable. In this study we evaluate in vitro the cytotoxic activity of three synthesized metallo-phthalocyanines with absorption bands in the red part of the spectrum: zinc-di-sulphonated phthalocyanine (ZnS IIPc), zinc-tri-sulphonated phthalocyanine (ZnS 3Pc) and zinc-tetrasulphonated phthalocyanine (ZnS 4Pc). Some cellular models have been used in this paper, in order to optimize the conditions of this method, as we are presenting in this paper (LSR-SF(SR) - transplantable sarcoma in rat induced by Rous sarcoma virus strain Schmidt-Ruppin; LSCC-SF(Mc29) - transplantable chicken hepatoma induced by the myelocytomatosis virus Mc29, MCF-7 cell line (human breast adenocarcinoma) derived from a patient with metastatic breast cancer, 8-MG-BA - glioblastoma multiforme 8-MG-BA, K562 - lymphoblastic human cell line, LLC-WRC 256 - Walker epithelial carcinoma. Activation of these photosensitizers retained in the cancerous cells, by red light emitted from a He-Ne laser at ?= 632.8 nm laser system, or by a diode laser emitting at 672 nm, produces a photochemical reaction that results in the selective destruction of tumor cells.

  18. Mechanisms of Resistance to Photodynamic Therapy

    PubMed Central

    Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

    2013-01-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

  19. Animal models for photodynamic therapy (PDT)

    PubMed Central

    Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.

    2015-01-01

    Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. PMID:26415497

  20. Optical delivery and monitoring of photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Bogaards, Arjun; Gertner, Mark; Davidson, Sean; Zhang, Kai; Netchev, George; Giewercer, David J.; Trachtenberg, John; Wilson, Brian C.

    2004-10-01

    Photodynamic therapy of recurrent prostate cancer is currently undergoing Phase II clinical trials with the vascular targeting drug TOOKAD. Proper PDT dosage requires sound estimates of the light fluence and drug concentration throughout the organ. The treatment requires multiple diffusing light delivery fibers placed in position according to a light dose treatment plan under ultrasound guidance. Fluence rate is monitored by multiple sensor fibers placed throughout the organ and in sensitive organs near the prostate. The combination of multiple light delivery and fluence sensor fibers is used to estimate the optical properties of the tissue and to provide a general fluence map throughout the organ. This fluence map is then used to estimate extent of photodynamic dose. Optical spectroscopy is used to monitor drug pharmacokinetics in the organ and blood hemodynamics within the organ. Further development of these delivery and monitoring techniques will permit full online monitoring of the treatment that will enable real-time patient-specific delivery of photodynamic therapy.

  1. Photodynamic therapy by in situ nonlinear photon conversion

    NASA Astrophysics Data System (ADS)

    Kachynski, A. V.; Pliss, A.; Kuzmin, A. N.; Ohulchanskyy, T. Y.; Baev, A.; Qu, J.; Prasad, P. N.

    2014-06-01

    In photodynamic therapy, light is absorbed by a therapy agent (photosensitizer) to generate reactive oxygen, which then locally kills diseased cells. Here, we report a new form of photodynamic therapy in which nonlinear optical interactions of near-infrared laser radiation with a biological medium in situ produce light that falls within the absorption band of the photosensitizer. The use of near-infrared radiation, followed by upconversion to visible or ultraviolet light, provides deep tissue penetration, thus overcoming a major hurdle in treatment. By modelling and experiment, we demonstrate activation of a known photosensitizer, chlorin e6, by in situ nonlinear optical upconversion of near-infrared laser radiation using second-harmonic generation in collagen and four-wave mixing, including coherent anti-Stokes Raman scattering, produced by cellular biomolecules. The introduction of coherent anti-Stokes Raman scattering/four-wave mixing to photodynamic therapy in vitro increases the efficiency by a factor of two compared to two-photon photodynamic therapy alone, while second-harmonic generation provides a fivefold increase.

  2. Photodynamic Therapy for the Endodontic Treatment of a Traumatic Primary Tooth in a Diabetic Pediatric Patient

    PubMed Central

    de Sant’Anna, Giselle

    2014-01-01

    Conservation of deciduous teeth with pulp alterations caused by caries or trauma is a major therapeutic challenge in pediatric dentistry. It is essential that the sanitizers used in root canal procedures perform well in eliminating bacteria. Antimicrobial photodynamic therapy (PDT) is an emerging and promising adjuvant therapy for endodontic treatment in an attempt to eliminate microorganisms persistent after chemomechanical preparation. This paper reports the case of a five-year-old male with type I diabetes mellitus, presenting the need for pulp therapy in maxillary primary left central incisor due to injury. The proposed treatment included the use of PDT for decontamination of root canals with the application of 50 ?g/mL of methylene blue dye for 3-5 minutes and 40 J/cm2 as energy density, taking into account the need for tissue penetration and effec-tiveness of PDT inside the dentinal tubules. PMID:25024841

  3. Anti-tumor effects on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice

    NASA Astrophysics Data System (ADS)

    Lee, Kyu Wan; Wen, Lan Ying; Bae, Su Mi; Park, Choong Hak; Jeon, Woo Kyu; Lee, Doo Yun; Ahn, Woong Shick

    2009-06-01

    The effects of As4O6 were studied as adjuvant on photodynamic therapy. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. In vitro experiments, cell proliferation and morphology were determined by MTT assay. Also, quantitative PCR array was performed to study the synergetic mechanism. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows an inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P < 0.05). Antiproliferative effect of combination treatment was significantly higher than those of TC-1 cells treated with either photodynamic therapy or As4O6 (62.4 and 52.5% decrease, respectively, compared to photodynamic therapy or As4O6 alone, P < 0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% compared to vehicle-only treated TC-1 cells (P < 0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly- 12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth.

  4. Spectrophotometric characterization of useful dyes in laser photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Danaila, Leon; Pascu, Mihail-Lucian; Popescu, Alina; Pascu, Mihaela O.; Ion, Rodica-Mariana

    2000-02-01

    This paper present the physico-chemical properties of some synthetic porphyrin dyes obtained at ZECASIN SA. We have measured the absorption, excitation and fluorescence spectra of these dyes in different solvents. From them we have concluded that the most reliable due for our studies concerning the photodynamic therapy with UV lasers is Zn II- tetrakis-sulfonatophenyl porphyrin.

  5. Photodynamic therapy: tumor targeting with adenoviral proteins.

    PubMed

    Allen, C M; Sharman, W M; La Madeleine, C; Weber, J M; Langlois, R; Ouellet, R; van Lier, J E

    1999-10-01

    A brief summary of the mechanisms involved in photodynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocyanines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus penton base proteins contain the arginine-glycine-aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteins via one or two caproic acid spacer chains (A1 or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L-tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption and in vitro photocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT-6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2-protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1 preparations. The penton base-AlPcS4A2 derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT-6 tumor implants demonstrated that the free AlPcS4A2 induced complete tumor regression at a dose of 1 mumol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adj. A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2 required 0.5 mumol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT. PMID:10546549

  6. Effects of telomerase expression on photodynamic therapy of Barrett's esophagus

    NASA Astrophysics Data System (ADS)

    Wang, Kenneth K.; Anderson, Marlys; Buttar, Navtej; WongKeeSong, Louis-Michel; Borkenhagen, Lynn; Lutzke, Lori

    2003-06-01

    Photodynamic therapy has been applied to Barrett's esophagus and has been shown in prospective randomized studies to eliminate dysplasia as well as decrease the occurrence of cancer. However, the therapy isnot always effective and there are issues with residual areas of Barrett's mucosa despite therapy. There has not been a good explanation for these residual areas and they seem to imply that there may exist a biological mechanisms by which these cells may be resistant to photodynamic therapy. It was our aim to determine if known abnormalities in Barrett's mucosa could be correlated with the lack of response of some of these tissues. We examined the tissue from mulitpel patients who had resonse to therapy as well as those who did not respond. We assessed the tissue for p53 mutations, inactivatino of p16, ploidy status, cell proliferation, telomerase activity, and degree of dysplasia. Interestingly, the only genetic marker than was found to be correlated with lack of reonse was p53 and telomerase activity. This suggests that cells that have lost mechanisms for cell death such as apoptosis or telomere shortengin may be more resistant to photodynamic therapy. In this study, we examined patients before and after PDT for telomerase activity.

  7. Photodynamic Therapy in Treatment of Oral Lichen Planus

    PubMed Central

    Mostafa, Diana; Tarakji, Bassel

    2015-01-01

    Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: “photodynamic therapy” and “treatment of oral lichen planus”. Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP. PMID:25883701

  8. Anticancer photodynamic therapy based on the use of a microsystem

    NASA Astrophysics Data System (ADS)

    Jastrzebska, E.; Bulka, N.; Zukowski, K.; Chudy, M.; Brzozka, Z.; Dybko, A.

    2015-07-01

    The paper presents the evaluation of photodynamic therapy (PDT) procedures with an application of a microsystem. Two cell lines were used in the experiments, i.e. human lung carcinoma - A549 and normal human fetal lung fibroblast MRC5. Mono-, coculture and mixed cultures were performed in a microsystem at the same time. The microsystem consisted of a concentration gradient generator (CGG) which generates different concentrations of a photosensitizer, and a set of microchambers for cells. The microchambers were linked by microchannels of various length in order to allow cells migration and in this way cocultures were created. Transparent materials were used for the chip manufacture, i.e. glass and poly(dimethylsiloxane). A high power LED was used to test photodynamic therapy effectiveness in the microsystem.

  9. Simultaneous two-photon excitation of photodynamic therapy agents

    SciTech Connect

    Wachter, E.A.; Fisher, W.G. |; Partridge, W.P.; Dees, H.C.; Petersen, M.G.

    1998-01-01

    The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.

  10. Novel flexible light diffuser and irradiation properties for photodynamic therapy.

    PubMed

    Selm, Baerbel; Rothmaier, Markus; Camenzind, Martin; Khan, Tania; Walt, Heinrich

    2007-01-01

    Many current light diffusers for photodynamic therapy are inflexible, and the applied light dose is difficult to adjust during treatment, especially on complex body surfaces. A thin and flexible luminous textile is developed using plastic optical fibers as a light distributor. The textile diffuser is evaluated for flexibility, irradiance, brightness distribution, and temperature rise with a 652-nm laser set to 100 mW. The bending force of the textile diffuser resembles a defined optical film. On the textile surface, an average output power of 3.6+/-0.6 mWcm(2) is measured, corresponding to a transmission rate of 40+/-3.8% on an area of 11 cm(2). Aluminum backing enhances the irradiance to the face (treatment side). The measured brightness distribution seems to lie within a range similar to other photodynamic therapy (PDT) devices. A power setting of 100 mW increases the temperature of the textile diffuser surface of up to 27 degrees C, and 1 W raises the temperature above 40 degrees C. Results confirm that the flexible textile diffuser supplies suitable radiation for low fluence rate photodynamic therapy on an area of several cm(2). PMID:17614732

  11. Fluorescence-guided resections and photodynamic therapy for malignant gliomas using 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Baumgartner, Reinhold; Stummer, Walter; Olzowy, Bernhard; Mehrkens, Jan H.; Tonn, Joerg C.; Reulen, Hans J.

    2005-04-01

    Oral application of 20 mg/kg bw of 5-aminolevulinic acid results in a highly specific accumulation of fluorescent and phototoxic Protoporphyrin IX in malignant glioma tissue. Surgical removal with fluorescence guidance is studied in a phase III clinical trial, adjuvant Photodynamic Therapy (PDT) to the surgical cavity is in phase II and for interstitial PDT of recurrent gliomas, a phase I/II study has started. Fluorescence guided resections have been shown to be safe and effective in augmenting neurosurgical removal of malignant gliomas in 52 consecutive patients. Intra-operative fluorescence spectroscopy showed statistically significant higher sensitizer accumulation in vital brain tumor versus the infiltration zone and in the infiltration zone versus adjacent normal brain, which contained very little PPIX. This is promisingly exploited for PDT - both to the surgical cavity by surface irradiation and for stereotactically guided interstitial irradiation.

  12. Adjuvant endocrine therapy for premenopausal women with early breast cancer.

    PubMed

    Bao, Ting; Davidson, Nancy E

    2007-01-01

    Adjuvant endocrine therapy is a pivotal component of treatment for premenopausal women with early-stage hormone receptor-positive breast cancer. Currently, the standard endocrine therapy for premenopausal women is tamoxifen; a role for ovarian suppression or ablation has also been identified. Uncertainty remains about the optimal use of endocrine therapy in this setting. The role of ovarian suppression with tamoxifen or aromatase inhibitor, the optimal duration of adjuvant endocrine therapy and the utility of biomarkers and pharmacogenetic studies to select therapy are questions worthy of further investigation. PMID:18190722

  13. Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy.

    PubMed

    Li, Yiye; Wen, Tao; Zhao, Ruifang; Liu, Xixi; Ji, Tianjiao; Wang, Hai; Shi, Xiaowei; Shi, Jian; Wei, Jingyan; Zhao, Yuliang; Wu, Xiaochun; Nie, Guangjun

    2014-11-25

    Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy. PMID:25375193

  14. Optical imaging in photodynamic therapy: mechanisms and applications

    NASA Astrophysics Data System (ADS)

    Solban, Nicolas; Georgakoudi, Irene; Ortel, Bernhard; Lin, Charles P.; Hasan, Tayyaba

    2004-06-01

    Molecular excitation of photosensitizing agents provides reactive excited states, which can initiate chemical reactions, but it can also lead to molecular relaxation via radiative photophysical processes, providing the basis for fluorescence diagnostics. The best-known example of the former is Photodynamic Therapy (PDT), which is now approved for the treatment of a number of neoplastic and non-neoplastic pathologies. Although the concept of the use of photodynamic agents in diagnostics is as old as their use in therapy, the focused development of this aspect has been relatively recent. Typically, photodynamic agents have high triplet yields and relatively long triplet lifetimes (microsecond range), which allows them to interact and destroy molecular targets near them either directly or indirectly by producing other toxic molecular species. Associated with a high triplet yield is the fortunate attribute of most PDT agents in having low but finite fluorescence quantum yields. Fluorescence from these molecules may be used not only for diagnostics of disease de novo but also for guided surgery, PDT dosimetry and therapeutic monitoring. Other uses of fluorescence in PDT (not necessarily from the PDT agents) include the development of technologies that allow tracking of cells during treatment in vivo, studies of sub-cellular localization of molecules for mechanistic studies and photosensitizer tracking for specific targeting. An overview of studies on these aspects from different laboratories will be presented.

  15. Tumor vasculature targeted photodynamic therapy for enhanced delivery of nanoparticles.

    PubMed

    Zhen, Zipeng; Tang, Wei; Chuang, Yen-Jun; Todd, Trever; Zhang, Weizhong; Lin, Xin; Niu, Gang; Liu, Gang; Wang, Lianchun; Pan, Zhengwei; Chen, Xiaoyuan; Xie, Jin

    2014-06-24

    Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors' origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as "smart" carriers that site-specifically deliver (1)O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine. PMID:24806291

  16. European Dermatology Forum Guidelines on topical photodynamic therapy.

    PubMed

    Morton, Colin; Szeimies, Rolf-Markus; Sidoroff, Alexis; Wennberg, Ann-Marie; Basset-Seguin, Nicole; Calzavara-Pinton, Piergiacomo; Gilaberte, Yolanda; Hofbauer, Günther; Hunger, Robert; Karrer, Sigrid; Lehmann, Percy; Piaserico, Stefano; Ulrich, Claas; Braathen, Lasse

    2015-01-01

    Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines. PMID:26065545

  17. Photochemistry and Photobiology, 2005, 81: 14601468 Modeling of a Type II Photofrin-mediated Photodynamic Therapy

    E-print Network

    and luminal cancers by employing non-ionizing radiation of visible and near- infrared light (1). Compared-mediated Photodynamic Therapy Process in a Heterogeneous Tissue Phantom Xin-Hua Hu*1,2 , Yuanming Feng3 , Jun Q. Lu1.1562/2005-05-04-RA-513 ABSTRACT We present a quantitative framework to model a Type II photodynamic therapy (PDT

  18. Photodynamic Therapy with Motexafin Lutetium for Rectal Cancer: A Preclinical Model in the Dog

    E-print Network

    Yodh, Arjun G.

    Photodynamic Therapy with Motexafin Lutetium for Rectal Cancer: A Preclinical Model in the Dog H of rectal resection after motexafin lutetium-mediated photodynamic therapy. Methods. Ten mixed breed dogs received the photosensitizing agent motexafin lutetium (MLu, Pharmacyclics, Inc., Sunnyvale, CA) of 2 mg

  19. Optical dosimetry for interstitial photodynamic therapy

    SciTech Connect

    Arnfield, M.R.; Tulip, J.; Chetner, M.; McPhee, M.S. )

    1989-07-01

    An approach to photodynamic treatment of tumors is the interstitial implantation of fiber optic light sources. Dosimetry is critical in identifying regions of low light intensity in the tumor which may prevent tumor cure. We describe a numerical technique for calculating light distributions within tumors, from multiple fiber optic sources. The method was tested using four translucent plastic needles, which were placed in a 0.94 X 0.94 cm grid pattern within excised Dunning R3327-AT rat prostate tumors. A cylindrical diffusing fiber tip, illuminated by 630 nm dye laser light was placed within one needle and a miniature light detector was placed within another. The average penetration depth in the tumor region between the two needles was calculated from the optical power measured by the detector, using a modified diffusion theory. Repeating the procedure for each pair of needles revealed significant variations in penetration depth within individual tumors. Average values of penetration depth, absorption coefficient, scattering coefficient, and mean scattering cosine were 0.282 cm, 0.469 cm-1, 250 cm-1 and 0.964, respectively. Calculated light distributions from four cylindrical sources in tumors gave reasonable agreement with direct light measurements using fiber optic probes.

  20. A Comprehensive Tutorial on In Vitro Characterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

    PubMed Central

    Maisch, Tim; Berneburg, Mark; Plaetzer, Kristjan

    2013-01-01

    In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research. PMID:23762860

  1. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy

    E-print Network

    Collins, James J.

    Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy Timothy K. Lua, there is a pressing need for new antibacterial therapies that can be readily designed and implemented. In this work, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly

  2. Spectroscopic evaluation of photodynamic therapy of the intraperitoneal cavity

    NASA Astrophysics Data System (ADS)

    Finlay, Jarod C.; Sandell, Julia L.; Zhu, Timothy C.; Lewis, Robert; Cengel, Keith A.; Hahn, Stephen M.

    2010-02-01

    We present the results of spectroscopic measurements of diffuse reflectance and fluorescence before and after photodynamic therapy of healthy canine peritoneal cavity. Animals were treated intra-operatively after iv injection of the benzoporphyrin derivative (BPD). The small bowel was treated using a uniform light field projected by a microlens-tipped fiber. The cavity was then filled with scattering medium and the remaining organs were treated using a moving diffuser. Diffuse reflectance and fluorescence measurements were made using a multi-fiber optical probe positioned on the surface of various tissues within the cavity before and after illumination. The measured data were analyzed to quantify hemoglobin concentration and oxygenation and sensitizer concentration.

  3. New Methods for the Clinical Enhancement of Photodynamic Therapy.

    PubMed

    Taub, Amy Forman; Schieber, Ann Cameron

    2015-11-01

    The prolonged incubation time of Photodynamic Therapy (PDT) as well as the need for two treatments to achieve high efficacy have motivated physicians to experiment with treatment parameters and PDT enhancements in order to maximize results and practicality. This review explores recent published strategies including occlusion, temperature elevation, pretreatment with topical 5-FU, and microneedle or laser-assisted reduction of the stratum corneum barrier. All of these innovations improve efficacy, reduce the need for multiple treatments or both, although there are concomitant increases in post-procedure side effects.

    J Drugs Dermatol. 2015;14(11):1329-1334. PMID:26580883

  4. Photodynamic therapy of tumor-associated pathology of uterine cervix

    NASA Astrophysics Data System (ADS)

    Novikova, E. G.; Trushina, O. I.; Sokolov, V. V.; Filonenko, E. V.

    2005-08-01

    We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photoheme" in 56 patients - 44 women with pre-cancerous lesions of cervix (group 1) and 12 women with early cervical cancer (group 2). The results were as follows: group 1 - c omplete regression - 3 7 ( 84%), p artial regression - 4 ( 9,%), s tabilization - 2 (4,6%), progression -1 (2,3%); group 2 - complete regression - 8 (66,7%), partial regression - 1 (8,3%), stabilization - 3 (25%). Anti-viral effect was registered in 38 (90,4%) cases after first procedure, in 4 cases - after second procedure.

  5. 3D Monte Carlo radiation transfer modelling of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Campbell, C. Louise; Christison, Craig; Brown, C. Tom A.; Wood, Kenneth; Valentine, Ronan M.; Moseley, Harry

    2015-06-01

    The effects of ageing and skin type on Photodynamic Therapy (PDT) for different treatment methods have been theoretically investigated. A multilayered Monte Carlo Radiation Transfer model is presented where both daylight activated PDT and conventional PDT are compared. It was found that light penetrates deeper through older skin with a lighter complexion, which translates into a deeper effective treatment depth. The effect of ageing was found to be larger for darker skin types. The investigation further strengthens the usage of daylight as a potential light source for PDT where effective treatment depths of about 2 mm can be achieved.

  6. Fractional Resurfacing Aiding Photodynamic Therapy of a Recalcitrant Plantar Verruca

    PubMed Central

    Pope, Amy

    2008-01-01

    Fractional resurfacing has become a very popular laser modality in recent years, and photodynamic therapy (PDT) has become a mainstay of many practices treating a wide array of clinical entities. In this case report, we describe a recalcitrant verrucous lesion on the foot that is unresponsive to cryotherapy, pulsed dye laser, and pulsed dye laser with PDT. The lesion did, however, respond very well to the use of a fractional laser to enhance the penetration of the PDT photosensitizer and then responded to pulsed dye laser with PDT. Fractional resurfacing prior to PDT may be a novel dermatologic treatment approach, making PDT an even better treatment option in the future. PMID:21103307

  7. Enhancement of anti-tumor immunity by photodynamic therapy

    PubMed Central

    Brackett, Craig M.

    2009-01-01

    Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumors, resulting in cure of early disease and palliation of advanced disease. PDT was originally considered to be a local treatment; however, both pre-clinical and clinical studies have shown that local PDT treatment of tumors can enhance systemic anti-tumor immunity. The current state of investigations into the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this enhancement and the future of PDT as an immunotherapy are addressed in this review. PMID:19763892

  8. Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy

    PubMed Central

    Denis, Tyler GSt; Hamblin, Michael R

    2013-01-01

    Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. PMID:23641699

  9. Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma

    PubMed Central

    Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes

    2014-01-01

    Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma. PMID:25317253

  10. Photodynamic therapy in combating the causative microorganisms from endodontic infections

    PubMed Central

    de Oliveira, Bruna Paloma; Aguiar, Carlos Menezes; Câmara, Andréa Cruz

    2014-01-01

    Photodynamic therapy (PDT) is presented as a promising antimicrobial therapy that can eliminate microorganisms present in endodontic infections. This treatment is based on the use of a nontoxic photosensitizing agent followed by irradiation of a resonant light source being capable of generating highly reactive species that are harmful to microorganisms. The purpose of this paper is to review the dental literature about the main factors that encompass the use of PDT combined with endodontic treatment for decontamination of the root canal system. A literature search was performed using the following index databases: PubMed, ISI Web of Knowledge and MedLine, between 2000 and 2014, looking for studies regarding antimicrobial action of PDT and its application to endodontic therapy. It was observed that despite numerous promising results, it is still necessary to establish different parameters so that PDT can be used with maximum effectiveness in eliminating microorganisms that cause endodontic infections. PMID:25202228

  11. Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

    PubMed Central

    Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

    2015-01-01

    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

  12. Neoadjuvant or adjuvant therapy for gastric cancer

    PubMed Central

    Quéro, Laurent; Guillerm, Sophie; Hennequin, Christophe

    2015-01-01

    Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. In the United States, where a limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In Europe, intensified perioperative chemotherapy is commonly administered. In Japan and South Korea, postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. Several ongoing trials are currently evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as well as the place of targeted therapeutic agents in the treatment of advanced gastric carcinoma. PMID:26306142

  13. Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

    NASA Astrophysics Data System (ADS)

    Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

    2014-11-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

  14. [Azithromycin as an adjuvant therapy in cryptogenic organizing pneumonia].

    PubMed

    Vaz, A P; Morais, A; Melo, N; Caetano Mota, P; Souto Moura, C; Amorim, A

    2011-01-01

    There are literature data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP) as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy. A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500mg, on alternate days) as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week) with no documentation of adverse side effects. This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy. PMID:21652172

  15. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    SciTech Connect

    Bhatia, Sumita; Miller, Robert C. . E-mail: miller.robert@mayo.edu; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-10-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

  16. Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics

    PubMed Central

    Wang, Chao; Cheng, Liang; Liu, Zhuang

    2013-01-01

    Photodynamic therapy (PDT) is a non-invasive treatment modality for a variety of diseases including cancer. PDT based on upconversion nanoparticles (UCNPs) has received much attention in recent years. Under near-infrared (NIR) light excitation, UCNPs are able to emit high-energy visible light, which can activate surrounding photosensitizer (PS) molecules to produce singlet oxygen and kill cancer cells. Owing to the high tissue penetration ability of NIR light, NIR-excited UCNPs can be used to activate PS molecules in much deeper tissues compared to traditional PDT induced by visible or ultraviolet (UV) light. In addition to the application of UCNPs as an energy donor in PDT, via similar mechanisms, they could also be used for the NIR light-triggered drug release or activation of 'caged' imaging or therapeutic molecules. In this review, we will summarize the latest progresses regarding the applications of UCNPs for photodynamic therapy, NIR triggered drug and gene delivery, as well as several other UCNP-based cancer therapeutic approaches. The future prospects and challenges in this emerging field will be also discussed. PMID:23650479

  17. Quantum dot-tetrapyrrole complexes as photodynamic therapy agents

    NASA Astrophysics Data System (ADS)

    Martynenko, Irina; Visheratina, Anastasia; Kuznetsova, Vera; Orlova, Anna; Maslov, Vladimir; Fedorov, Anatoly; Baranov, Alexander

    2015-07-01

    Photophysical properties of complexes of semiconductor quantum dots with conventional photosensitizers for photodynamic therapy (tetrapyrroles) were investigated. A luminescent study of complexes in aqueous solutions was performed using spectral- and time-resolved luminescence spectroscopy. It was found that increasing the photosensitizer relative concentration in complexes resulted in sharp drop of the nonradiative energy transfer efficiency and the quantum yield of the photosensitizer photoluminescence. This fact indicates that additional channels of nonradiative energy dissipation may take place in the complexes. Using complexes of Al(OH)-sulphophthalocyanine with CdSe/ZnS quantum dots in the aqueous solution as an typical example, we have demonstrated that new channels of the energy dissipation may arise due to aggregation of the photosensitizer molecules upon formation of the complexes with quantum dots. We also demonstrated that use of methods of complex formation preventing aggregation of photosensitizers allows to conserve the high energy transfer efficiency and quantum yield of the acceptor photoluminescence in complexes in wide range of the photosensitizer concentrations. We believe that our study allows obtaining new information about the physical mechanisms of nonradiative energy transfer in quantum dots-tetrapyrrole complexes perspective for photodynamic therapy.

  18. Phthalocyanines And Their Sulfonated Derivatives As Photosensitizers In Photodynamic Therapy.

    NASA Astrophysics Data System (ADS)

    Riesz, Peter; Krishna, C. Murali

    1988-02-01

    Photodynamic therapy (PDT) of human tumors with hematoporphyrin derivative (HpD) has achieved encouraging results. However, HpD is a complex mixture whose composition varies in different preparations and with time of storage. The future promise of PDT for cancer treatment depends on the development of new chemically defined sensitizers which absorb more strongly than HpD in the 600-800 nm region. A shift to higher wavelengths is desirable since it allows increased light penetration in human tissues. In vivo, these sensitizers should be non-toxic, localize selectively in tumors and generate cytotoxic species upon illumination with a high quantum yield. These damaging species may be singlet oxygen (1O2) produced by the transfer of energy from the triplet state of the sensitizer to oxygen (Type II) or superoxide anion radicals formed by electron transfer to oxygen or substrate radicals generated by electron or hydrogen transfer directly from the sensitizer (Type I). The recent work of several groups indicating that phthalocyanines and their water soluble derivatives are promising candidates for PDT is reviewed. The photophysics, photochemistry, photosensitized killing of cultured mammalian cells and the use for in vivo photodynamic therapy of phthalocyanines is outlined. Our studies of the post-illumination photohemolysis of human red blood cells as a model system for membrane photomodification sensitized by phthalocyanine sulfonates are consistent with the predominant role of 1O2 as the damaging species.

  19. Physical and mathematical modeling of antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bürgermeister, Lisa; López, Fernando Romero; Schulz, Wolfgang

    2014-07-01

    Antimicrobial photodynamic therapy (aPDT) is a promising method to treat local bacterial infections. The therapy is painless and does not cause bacterial resistances. However, there are gaps in understanding the dynamics of the processes, especially in periodontal treatment. This work describes the advances in fundamental physical and mathematical modeling of aPDT used for interpretation of experimental evidence. The result is a two-dimensional model of aPDT in a dental pocket phantom model. In this model, the propagation of laser light and the kinetics of the chemical reactions are described as coupled processes. The laser light induces the chemical processes depending on its intensity. As a consequence of the chemical processes, the local optical properties and distribution of laser light change as well as the reaction rates. The mathematical description of these coupled processes will help to develop treatment protocols and is the first step toward an inline feedback system for aPDT users.

  20. Possibility for a full optical determination of photodynamic therapy outcome

    NASA Astrophysics Data System (ADS)

    Vollet-Filho, J. D.; Menezes, P. F. C.; Moriyama, L. T.; Grecco, C.; Sibata, C.; Allison, R. R.; Castro e Silva, O.; Bagnato, V. S.

    2009-05-01

    The efficacy of photodynamic therapy (PDT) depends on a variety of parameters: concentration of the photosensitizer at the time of treatment, light wavelength, fluence, fluence rate, availability of oxygen within the illuminated volume, and light distribution in the tissue. Dosimetry in PDT requires the congregation of adequate amounts of light, drug, and tissue oxygen. The adequate dosimetry should be able to predict the extension of the tissue damage. Photosensitizer photobleaching rate depends on the availability of molecular oxygen in the tissue. Based on photosensitizers photobleaching models, high photobleaching has to be associated with high production of singlet oxygen and therefore with higher photodynamic action, resulting in a greater depth of necrosis. The purpose of this work is to show a possible correlation between depth of necrosis and the in vivo photosensitizer (in this case, Photogem®) photodegradation during PDT. Such correlation allows possibilities for the development of a real time evaluation of the photodynamic action during PDT application. Experiments were performed in a range of fluence (0-450 J/cm2) at a constant fluence rate of 250 mW/cm2 and applying different illumination times (0-1800 s) to achieve the desired fluence. A quantity was defined (?) as the product of fluorescence ratio (related to the photosensitizer degradation at the surface) and the observed depth of necrosis. The correlation between depth of necrosis and surface fluorescence signal is expressed in ? and could allow, in principle, a noninvasive monitoring of PDT effects during treatment. High degree of correlation is observed and a simple mathematical model to justify the results is presented.

  1. Targeted photodynamic therapy for infected wounds in mice

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.; O'Donnell, David A.; Zahra, Touqir; Contag, Christopher H.; McManus, Albert T.; Hasan, Tayyaba

    2002-06-01

    Although many workers have used photodynamic therapy to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We report on the use of a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) that can penetrate the Gram (-) outer membrane together with red laser light to kill Escherichia coli and Pseudomonas aeruginosa infecting excisional wounds in mice. We used genetically engineered luminescent bacteria that allowed the infection to be imaged in mouse wounds using a sensitive CCD camera. Wounds were infected with 5x106 bacteria, followed by application of the conjugate in solution and illumination. There was a light-dose dependent loss of luminescence as measured by image analysis in the wound treated with conjugate and light, not seen in control wounds. This strain of E coli is non-invasive and the infection in untreated wounds spontaneously resolved in a few days and all wounds healed equally well showing the photodynamic treatment did not damage the host tissue. P aeruginosa is highly invasive and mice with untreated or control wounds all died while 90% of PDT treated mice survived. PDT may have a role to play in the rapid treatment of infected wounds in view of the worldwide rise in antibiotic resistance.

  2. Photosensitizer nanocarriers modeling for photodynamic therapy applied to dermatological diseases

    NASA Astrophysics Data System (ADS)

    Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

    2011-02-01

    Photodynamic Therapy involves the therapeutic use of photosensitizers in combination with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell death. This technique has become widely used in medicine to treat tumors and other nonmalignant diseases. However, there are several factors related to illumination or the photosensitizer that limit an optimal treatment outcome. The use of nanoparticles (NP) for PDT has been proposed as a solution to current shortcomings. In this way, there are NPs that act as carriers for photosensitizers, NPs that absorb the light and transfer the energy to the photosensitizer and NPs that are themselves photodynamically active. In dermatology, the use of topical photosensitizers produces a time dependent inhomogeneous distribution within the tumor, where the stratum corneum is the main barrier to the diffusion of the photosensitizer to the deeper layers of skin. This produces an insufficient photosensitizer accumulation in tumor tissues and therefore, a low therapeutic efficiency in the case of deep lesions. This work focuses in the use of NPs as photosensitizer carriers to improve the actual topical drug distribution in malignant skin tissues. We present a mathematical model of PS distribution in tumor tissue using NPs that takes into account parameters related to nanoparticles binding. Once the concentration profile of NPs into tissue is obtained, we use a photochemical model which allows us to calculate the temporal evolution of reactive oxygen species according to PS distribution calculated previously from NPs profile.

  3. Porphyrin-based Nanostructure-Dependent Photodynamic and Photothermal Therapies

    NASA Astrophysics Data System (ADS)

    Jin, Cheng S.

    This thesis presents the investigation of nanostructure-dependent phototherapy. We reviewed the liposomal structures for delivery of photosensitizers, and introduced a novel class of phototransducing liposomes called "porphysomes". Porphysomes are self-assembled from high packing density of pyropheophorbide alpha-conjugated phospholipids, resulting in extreme self-quenching of porphyrin fluorescence and comparable optical absorption to gold nanoparticles for high photothermal efficiency. We demonstrated this self-assembly of porphyrin-lipid conjugates converts a singlet oxygen generating mechanism (photodynamic therapy PDT activity) of porphyrin to photothermal mechanism (photothermal therapy PTT activity). The efficacy of porphysome-enhanced PTT was then evaluated on two pre-clinical animal models. We validated porphysome-enabled focal PTT to treat orthotopic prostate cancer using MRI-guided focal laser placement to closely mimic the current clinic procedure. Furthermore, porphysome-enabled fluorescence-guided transbronchial PTT of lung cancer was demonstrated in rabbit orthotopic lung cancer models, which led to the development of an ultra-minimally invasive therapy for early-stage peripheral lung cancer. On the other hand, the nanostructure-mediated conversion of PDT to PTT can be switched back by nanoparticle dissociation. By incorporating folate-conjugated phospholipids into the formulation, porphysomes were internalized into cells rapidly via folate receptor-mediated endocytosis and resulted in efficient disruption of nanostructures, which turned back on the photodynamic activity of densely packed porphyrins, making a closed loop of conversion between PDT and PTT. The multimodal imaging and therapeutic features of porphysome make it ideal for future personalized cancer treatments.

  4. Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

    SciTech Connect

    Gold, Douglas G.; Miller, Robert C. Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

    2009-09-01

    Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

  5. ACR Appropriateness Criteria® Adjuvant Therapy in Vulvar Cancer.

    PubMed

    Jolly, Shruti; Soni, Payal; Gaffney, David K; Biagioli, Matthew; Elshaikh, Mohamed A; Jhingran, Anuja; Kidd, Elizabeth; Lee, Larissa J; Li, Linna; Moore, David H; Rao, Gautam G; Wahl, Andrew O; Williams, Ned L; Yashar, Catheryn M; Small, William

    2015-11-01

    These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy. PMID:26568534

  6. Experimental use of photodynamic therapy in high grade gliomas: a review focused on 5-aminolevulinic acid.

    PubMed

    Tetard, Marie-Charlotte; Vermandel, Maximilien; Mordon, Serge; Lejeune, Jean-Paul; Reyns, Nicolas

    2014-09-01

    Photodynamic therapy (PDT) consists of a laser light exposure of tumor cells photosensitized by general or local administration of a pharmacological agent. Nowadays, PDT is a clinically established modality for treatment of many cancers. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven its rational in fluoro-guided resection of malignant gliomas due to a selective tumor uptake and minimal skin sensitization. Moreover, the relatively specific accumulation of photosensitizing PPIX within the tumor cells has gained interest in the PDT of malignant gliomas. Several experimental and clinical studies have then established ALA-PDT as a valuable adjuvant therapy in the management of malignant gliomas. However, the procedure still requires optimizations in the fields of tissue oxygenation status, photosensitizer concentration or scheme of laser light illumination. In this extensive review, we focused on the methods and results of ALA-PDT for treating malignant gliomas in experimental conditions. The biological mechanisms, the effects on tumor and normal brain tissue, and finally the critical issues to optimize the efficacy of ALA-PDT were discussed. PMID:24905843

  7. Role of inflammatory cytokines in the response of solid cancers to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai; Cecic, Ivana; Dougherty, Graeme J.

    2001-04-01

    Photodynamic therapy (PDT) elicits a strong acute inflammatory response that has both local and systemic (acute phase response) attributes. The insult mediated by PDT-induced oxidative stress at the targeted site triggers a complex multifactorial response engaging host defence mechanisms associated with the inflammatory process to participate in the eradication of the treated tumor. Inflammatory cytokines are important mediators of critical events in this process as they regulate the activity of inflammatory, endothelial and other cells. The initial stimulus for enhanced production and release of cytokines likely originates from several types of events, such as activated transcription factors and complement deposition. The PDT-induced complement activation appears to be directly linked to the enhanced expression of various cytokines, including chemokines such as KC (in mouse models), and classic inflammatory cytokines such as IL-1?, TNF-? , IL-6 and IL-10. A variety of interventions that modulate the activity of particular cytokines performed in conjunction with PDT were shown to influence the therapy outcome. The treatments such as using blocking antibodies and local or systemic cytokine delivery may either reduce or dramatically improve the curative effect of PDT. The inflammatory and related cytokines that at present appear particularly interesting and merit further investigation for use as adjuvants to PDT are IL-3, IL-8, IL-15, TNF-?, IFN-?, G-CSF and GM-CSF.

  8. Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies.

    PubMed

    Broekgaarden, Mans; Weijer, Ruud; van Gulik, Thomas M; Hamblin, Michael R; Heger, Michal

    2015-12-01

    Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies such as surgery, chemotherapy, and radiotherapy. PDT comprises the administration of a photosensitizer, its accumulation in tumor tissue, and subsequent irradiation of the photosensitizer-loaded tumor, leading to the localized photoproduction of reactive oxygen species (ROS). The resulting oxidative damage ultimately culminates in tumor cell death, vascular shutdown, induction of an antitumor immune response, and the consequent destruction of the tumor. However, the ROS produced by PDT also triggers a stress response that, as part of a cell survival mechanism, helps cancer cells to cope with the PDT-induced oxidative stress and cell damage. These survival pathways are mediated by the transcription factors activator protein 1 (AP-1), nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor 1 (HIF-1), nuclear factor ?B (NF-?B), and those that mediate the proteotoxic stress response. The survival pathways are believed to render some types of cancer recalcitrant to PDT and alter the tumor microenvironment in favor of tumor survival. In this review, the molecular mechanisms are elucidated that occur post-PDT to mediate cancer cell survival, on the basis of which pharmacological interventions are proposed. Specifically, pharmaceutical inhibitors of the molecular regulators of each survival pathway are addressed. The ultimate aim is to facilitate the development of adjuvant intervention strategies to improve PDT efficacy in recalcitrant solid tumors. PMID:26516076

  9. Photodynamic therapy in dermatology: past, present, and future

    NASA Astrophysics Data System (ADS)

    Darlenski, Razvigor; Fluhr, Joachim W.

    2013-06-01

    Photodynamic therapy (PDT) is a noninvasive therapeutic method first introduced in the field of dermatology. It is mainly used for the treatment of precancerous and superficial malignant skin tumors. Today PDT finds new applications not only for nononcologic dermatoses but also in the field of other medical specialties such as otorhinolaryngology, ophthalmology, neurology, gastroenterology, and urology. We are witnessing a broadening of the spectrum of skin diseases that are treated by PDT. Since its introduction, PDT protocol has evolved significantly in terms of increasing method efficacy and patient safety. In this era of evidence-based medicine, it is expected that much effort will be put into creating a worldwide accepted consensus on PDT. A review on the current knowledge of PDT is given, and the historical basis of the method's evolution since its introduction in the 1900s is presented. At the end, future challenges of PDT are focused on discussing gaps that exist for research in the field.

  10. Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers.

    PubMed

    Doshi, Mona; Gesquiere, Andre J

    2015-01-01

    In this article a method for the fabrication and reproducible in-vitro evaluation of conducting polymer nanoparticles blended with fullerene as the next generation photosensitizers for Photodynamic Therapy (PDT) is reported. The nanoparticles are formed by hydrophobic interaction of the semiconducting polymer MEH-PPV (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) with the fullerene PCBM (phenyl-C61-butyric acid methyl ester) in the presence of a non-compatible solvent. MEH-PPV has a high extinction coefficient that leads to high rates of triplet formation, and efficient charge and energy transfer to the fullerene PCBM. The latter processes enhance the efficiency of the PDT system through fullerene assisted triplet and radical formation, and ultrafast deactivation of MEH-PPV excited stated. The results reported here show that this nanoparticle PDT sensitizing system is highly effective and shows unexpected specificity to cancer cell lines. PMID:26556528

  11. TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wilson, Brian C.; Patterson, Michael S.

    2008-05-01

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components—light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

  12. Mechanisms of vessel damage in photodynamic therapy (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Fingar, Victor H.; Wieman, Thomas J.

    1992-06-01

    Vessel constriction and platelet aggregation are observed within the first minutes of light exposure to photosensitized tissues and lead to blood flow stasis, tissue hypoxia, and nutrient depravation. The mechanism for these vessel changes remains unknown, although the release of eicosanoids is implicated. We propose the following hypothesis: Photodynamic therapy results in specific perturbations of endothelial cells which results in a combination of membrane damage, mitochondrial damage, and rearrangement of cytoskeletal proteins. This results in cellular stress which leads to interruption of tight junctions along the endothelium and cell rounding. Cell rounding exposes the basement membrane proteins causing activation of platelets and leukocytes. Activated platelets and leukocytes release thromboxane and other eicosanoids. These eicosanoids induce vasoconstriction, platelet aggregation, increases in vessel permeability, and blood flow stasis.

  13. Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kempa, Marta; Kozub, Patrycja; Kimball, Joseph; Rojkiewicz, Marcin; Ku?, Piotr; Gryczy?ski, Zugmunt; Ratuszna, Alicja

    2015-07-01

    This research evaluated the suitability of synthetic photosensitizers for their use as potential photosensitizers in photodynamic therapy using steady state and time-resolved spectroscopic techniques. Four tetraphenylporphyrin derivatives were studied in ethanol and dimethyl sulfoxide. The spectroscopic properties namely electronic absorption and emission spectra, ability to generate singlet oxygen, lifetimes of the triplet state, as well as their fluorescence quantum yield were determined. Also time-correlated single photon counting method was used to precisely determine fluorescence lifetimes for all four compounds. Tested compounds exhibit high generation of singlet oxygen, low generation of fluorescence and they are chemical stable during irradiation. The studies show that the tested porphyrins satisfy the conditions of a potential drug in terms of physicochemical properties.

  14. Effects of verteporfin-mediated photodynamic therapy on endothelial cells

    NASA Astrophysics Data System (ADS)

    Kraus, Daniel; Chen, Bin

    2015-03-01

    Photodynamic therapy (PDT) is a treatment modality in which cytotoxic reactive oxygen species are generated from oxygen and other biological molecules when a photosensitizer is activated by light. PDT has been approved for the treatment of cancers and age-related macular degeneration (AMD) due to its effectiveness in cell killing and manageable normal tissue complications. In this study, we characterized the effects of verteporfin-PDT on SVEC mouse endothelial cells and determined its underlying cell death mechanisms. We found that verteporfin was primarily localized in mitochondria and endoplasmic reticulum (ER) in SVEC cells. Light treatment of photosensitized SVEC cells induced a rapid onset of cell apoptosis. In addition to significant structural damages to mitochondria and ER, verteporfin-PDT caused substantial degradation of ER signaling molecules, suggesting ER stress. These results demonstrate that verteporfin-PDT triggered SVEC cell apoptosis by both mitochondrial and ER stress pathways. Results from this study may lead to novel therapeutic approaches to enhance PDT outcome.

  15. Blue laser system for photo-dynamic therapy

    NASA Astrophysics Data System (ADS)

    Dabu, R.; Carstocea, B.; Blanaru, C.; Pacala, O.; Stratan, A.; Ursu, D.; Stegaru, F.

    2007-03-01

    A blue laser system for eye diseases (age related macular degeneration, sub-retinal neo-vascularisation in myopia and presumed ocular histoplasmosis syndrome - POHS) photo-dynamic therapy, based on riboflavin as photosensitive substance, has been developed. A CW diode laser at 445 nm wavelength was coupled through an opto-mechanical system to the viewing path of a bio-microscope. The laser beam power in the irradiated area is adjustable between 1 mW and 40 mW, in a spot of 3-5 mm diameter. The irradiation time can be programmed in the range of 1-19 minutes. Currently, the laser system is under clinic tests.

  16. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

    NASA Astrophysics Data System (ADS)

    Kishen, Anil; George, Saji

    2013-02-01

    In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

  17. Photodynamic therapy with verteporfin: a new treatment in ophthalmology.

    PubMed

    Michels, S; Schmidt-Erfurth, U

    2001-12-01

    Photodynamic therapy (PDT) with verteporfin is a new treatment modality in ophthalmology that has previously shown its effectiveness in treatment of a variety of neoplastic pathologies. In this therapeutic approach, the photosensitizer verteporfin is activated by non-thermal laser light to obtain closure of neovascular structures. Preclinical and clinical studies have indicated that PDT is a safe, selective, and effective treatment for choroidal neovascularization in age-related macular degeneration. No significant damage to the neurosensory retina was found, which explains why PDT does not cause loss of visual acuity and may be used in a larger population than laser photocoagulation. This review summarizes the mechanisms of action of PDT, and the results of preclinical and clinical studies in ophthalmology. PMID:15513441

  18. Photodynamic therapy of cancer with the photosensitizer PHOTOGEM

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Filonenko, E. V.; Sukhin, Garry M.; Yakubovskaya, Raisa I.; Belous, T. A.; Zharkova, Natalia N.; Kozlov, Dmitrij N.; Smirnov, V. V.

    1995-01-01

    The first clinical trials of photodynamic therapy (PDT) in Russia were started in P. A. Hertzen Moscow Research Oncology Institute in October of 1992. Up to now, 61 patients with primary or recurrent malignant tumors of the larynx (3), trachea (1), bronchus (11), nose (1), mouth (3), esophagus (12), vagina and uterine cervix (3), bladder (2), skin (6), and cutaneous and subcutaneous metastases of breast cancer and melanomas (6) have been treated by PDT with the photosensitizer Photogem. At least partial tumor response was observed in all of the cases, but complete remission indicating no evident tumors has been reached in 51% of the cases. Among 29 patients with early and first stage cancer 14 patients had multifocal tumors. Complete remission of tumors in this group reached 86%.

  19. Photodynamic therapy of head and neck cancer with different sensitizers

    NASA Astrophysics Data System (ADS)

    Vakoulovskaya, Elena G.; Shental, Victor V.; Abdoullin, N. A.; Kuvshinov, Yury P.; Tabolinovskaia, T. D.; Edinak, N. J.; Poddubny, Boris K.; Kondratjeva, T. T.; Meerovich, Gennadii A.; Stratonnikov, Alexander A.; Linkov, Kirill G.; Agafonov, Valery V.

    1997-12-01

    This paper deals with the results of clinical trials for sulfated aluminum phthalocyanine (PHS) (Photosens, Russia; Photogeme (PG) in Russia. The results of photodynamic therapy (PDT) of head and neck tumors (HNT), side effects and ways of their correction and prevention, as well as possibility to work out less toxic regimes of PDT with photosense, choice of laser and type of irradiation are discussed. PDT have been provided in 79 patients with different head and neck tumors. Efficacy of PDT depended on tumor size and its histological type. Undesirable changes in plasma content of antioxidants by means of high pressure liquid chromatography (HLPC) have been found in patients after PHS injection. Influence of short-term and long-term supplementation with beta-carotene and vitamin E on this parameters are discussed.

  20. Mitochondria-involved apoptosis induced by MPPa mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Tian, Y. Y.; Xu, D. D.; Tian, X.; Cui, F. A.; Yuan, H. Q.; Leung, W. N.

    2008-10-01

    Numerous new photosensitizers are now in various stages of trials demonstrating the broad applicability of Photodynamic therapy (PDT). However, only a handful of photosensitizers have received regulatory approval. Lack of effective photosensitizers has become a major limit for extensive application of PDT. Our previous study showed MPPa to be a good photosensitizer candidature, MPPa-PDT can lead PC-3M cell line to death mainly via apoptotic way both in vitro and in vivo, and part of the mechanism was investigated. Mitochondria may play a key role in the process, in order to further elucidate the mechanism, we investigated the level of ROS, GSH, NO, Ca2+, mitochondrial membrane potential, as well as cytochrome C. All in all, ROS production, depletion of GSH, and the activation of ROS downstream, such as mitochondria depolarization, cytochrome C release, were detected in our study. The results provide a mechanism by which oxidative stress provokes apoptosis of PC-3M cells.

  1. Photodynamic therapy: Theoretical and experimental approaches to dosimetry

    NASA Astrophysics Data System (ADS)

    Wang, Ken Kang-Hsin

    Singlet oxygen (1O2) is the major cytotoxic species generated during photodynamic therapy (PDT), and 1O 2 reactions with biological targets define the photodynamic dose at the most fundamental level. We have developed a theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O 2) consumption and transport and microscopic 1O 2 dose deposition during PDT in vivo. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O 2 saturation within vessels, irreversible photosensitizer degradation due to photobleaching, therapy-induced blood flow decrease and the microscopic distributions of 3O2 and 1O 2 dose deposition under various irradiation conditions. mTHPC, a promising photosensitizer for PDT, is approved in Europe for the palliative treatment of head and neck cancer. Using the theoretical model and informed by intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions for mTHPC-PDT. Our results demonstrate that the 1O 2 dose to the tumor volume does not track even qualitatively with long-term tumor responses. Thus, in this evaluation of mTHPC-PDT, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary. In addition to the case study of mTHPC-PDT, we also use the mathematical model to simulate clinical photobleaching data, informed by a possible blood flow reduction during treatment. In a recently completed clinical trial at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma received topical application of 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm-2 . Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by fluorescence spectroscopy. We successfully simulate the in vivo photobleaching of PpIX in this patient population over a wide range of irradiances using the PDT model. For most cases, the rate of bleaching slows as treatment progresses, leaving a fraction of the PpIX unbleached despite sustained irradiation. To account for this feature, the model predicts that incorporation of ALA-PDT-induced blood flow reduction is necessary. In addition to using the theoretical method to understand the dose deposited by photodynamic therapy, experimentally, we propose a potential dose metric for Pc 4-PDT. Pc 4 is a promising second generation photosensitizer that is now in Phase I clinical trials for the treatment of cutaneous lesions. We have observed a significant irradiation-induced increase in Pc 4 fluorescence in tumor cell monolayers. The amount of the fluorescence increase observed in vitro strongly correlates to the cell death and mitochondrial swelling reported by the clonogenic cell survival assay and light scattering measurements, respectively. Based on those biological responses, we anticipate that irradiation-induced fluorescence enhancement in Pc 4-PDT may be a potential dose metric.

  2. Current evidence and applications of photodynamic therapy in dermatology

    PubMed Central

    Wan, Marilyn T; Lin, Jennifer Y

    2014-01-01

    In photodynamic therapy (PDT) a photosensitizer – a molecule that is activated by light – is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT. PMID:24899818

  3. The Disinfecting Efficacy of Root Canals with Laser Photodynamic Therapy

    PubMed Central

    Xhevdet, Aliu; Stubljar, David; Kriznar, Igor; Jukic, Tomislav; Skvarc, Miha; Veranic, Peter

    2014-01-01

    Introduction: Infecting microorganisms of the root canals are difficult to eliminate during endodontic treatment. In this study the effect of root canal disinfection with photodynamic therapy (PDT) at different time intervals in comparison to 2.5% sodium hypochlorite (NaOCl) irrigation and passive ultrasonic irrigation (PUI) in extracted teeth colonized with Enterococcus faecalis and Candida albicans was tested to assess which treatment reaches the best disinfection rate. Methods: One hundred and fifty-six extracted single-rooted teeth were collected, sterilized, and incubated with Enterococcus faecalis (ATCC 29212) and Candida albicans (ATCC 60193). The two groups were further divided into 6 groups depending on the treatment mode; HELBO®Endo Blue photosensitizer dye application followed by HELBO laser irradiation, with the output power 100 mW and emission of 660 nm, for a 1, 3 and 5 minutes, irrigation with 2.5% NaOCl, 10 second PUI with 2.5% NaOCl and control group. Flow cytometry and scanning electron microscopic (SEM) analysis were used to determine the effectiveness of the different disinfecting methods. Results: The different disinfecting methods had a significantly different effect on the percent of dead cells (p<0.001). A statistical significance of dead cells between organisms (p<0.001) was observed. Interaction between the disinfecting method and both of organisms had shown the statistical significance (p=0.045). Percent of dead cells in treatment groups were significantly higher compared to control group for both organisms (p<0.001). Conclusions: PUI still remains the most effective method for disinfection of infected root canals in endodontics compared to hand instrumentation for both microorganisms. SEM analysis only confirmed the results. Other results ex vivo suggested that prolonging the time from 1 to 5 minutes of PDT increased the number of killed microorganisms significantly, therefore longer times of photodynamic therapy were recommended. Irrigation with 2.5% NaOCl showed similar results to 5 min irradiation. PMID:25606335

  4. Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy.

    PubMed

    Yuan, Ahu; Yang, Bing; Wu, Jinhui; Hu, Yiqiao; Ming, Xin

    2015-07-01

    Application of photodynamic therapy for treating cancers has been restrained by suboptimal delivery of photosensitizers to cancer cells. Nanoparticle (NP)-based delivery has become an important strategy to improve tumor delivery of photosensitizers; however, the success is still limited. One problem for many NPs is poor penetration into tumors, and thus the photokilling is not complete. We aimed to use chemical conjugation method to engineer small NPs for superior cancer cell uptake and tumor penetration. Thus, Chlorin e6 (Ce6) was covalently conjugated to PAMAM dendrimer (generation 7.0) that was also modified by tumor-targeting RGD peptide. With multiple Ce6 molecules in a single nanoconjugate molecule, the resultant targeted nanoconjugates showed uniform and monodispersed size distribution with a diameter of 28 nm. The singlet oxygen generation efficiency and fluorescence intensity of the nanoconjugates in aqueous media were significantly higher than free Ce6. Targeted nanoconjugates demonstrated approximately 16-fold enhancement in receptor-specific cellular delivery of Ce6 into integrin-expressing A375 cells compared to free Ce6 and thus were able to cause massive cell killing at low nanomolar concentrations under photo-irradiation. In contrast, they did not cause significant toxicity up to 2 ?M in dark. Due to their small size, the targeted nanoconjugates could penetrate deeply into tumor spheroids and produced strong photo-toxicity in this 3-D tumor model. As a result of their great cellular delivery, small size, and lack of dark cytotoxicity, the nanoconjugates may provide an effective tool for targeted photodynamic therapy of solid tumors. PMID:25900441

  5. System for integrated interstitial photodynamic therapy and dosimetric monitoring

    NASA Astrophysics Data System (ADS)

    Johansson, Ann; Soto Thompson, Marcelo; Johansson, Thomas; Bendsoe, Niels; Svanberg, Katarina; Svanberg, Sune; Andersson-Engels, Stefan

    2005-04-01

    Photodynamic therapy for the treatment of cancer relies on the presence of light, sensitizer and oxygen. By monitoring these three parameters during the treatment a better understanding and treatment control could possibly be achieved. Here we present data from in vivo treatments of solid skin tumors using an instrument for interstitial photodynamic therapy with integrated dosimetric monitoring. By using intra-tumoral ALA-administration and interstitial light delivery solid tumors are targeted. The same fibers are used for measuring the fluence rate at the treatment wavelength, the sensitizer fluorescence and the local blood oxygen saturation during the treatment. The data presented is based on 10 treatments in 8 patients with thick basal cell carcinomas. The fluence rate measurements at 635 nm indicate a major treatment induced absorption increase, leading to a limited light penetration at the treatment wavelength. This leads to a far from optimal treatment since the absorption increase prevents peripheral tumor regions from being fully treated. An interactive treatment has been implemented assisting the physician in delivering the correct light dose. The absorption increase can be compensated for by either prolonging the treatment time or increasing the output power of each individual treatment fiber. The other parameters of importance, i.e. the sensitizer fluorescence at 705 nm and the local blood oxygen saturation, are monitored in order to get an estimate of the amount of photobleaching and oxygen consumption. Based on the oxygen saturation signal, a fractionized irradiation can be introduced in order to allow for a re-oxygenation of the tissue.

  6. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

    PubMed Central

    Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

    2013-01-01

    Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID:23550545

  7. Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

    PubMed Central

    Yoon, Il; Li, Jia Zhu

    2013-01-01

    The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo. PMID:23423543

  8. Adjuvant and Neoadjuvant Therapy for Breast Cancer

    MedlinePLUS

    ... therapy deprives breast cancer cells of the hormone estrogen , which many breast tumors need to grow. A ... hormonal treatment is the drug tamoxifen , which blocks estrogen's activity in the body. Studies have shown that ...

  9. Dendrimer porphyrin-coated gold nanoshells for the synergistic combination of photodynamic and photothermal therapy.

    PubMed

    Chung, Ui Seok; Kim, Joo-Ho; Kim, Byeonggwan; Kim, Eunkyoung; Jang, Woo-Dong; Koh, Won-Gun

    2016-01-01

    A dendrimer porphyrin (DP)-coated gold nanoshell (AuNS-DP) was prepared for the synergistic combination of photodyanmic and photothermal therapy. The resultant AuNS-DP successfully exhibited the generation of reactive oxygen species (ROS) as well as photothermal effect for the simultaneous application of photodynamic therapy (PDT) and photothermal therapy (PTT). PMID:26610400

  10. [Laparoscopic surgery and adjuvant therapy for colon cancer].

    PubMed

    Kubicka, Stefan; Geissler, Michael; Bruch, Hans-Peter; Trarbach, Tanja

    2009-01-01

    At present, about 10% of all oncological procedures in the colon are carried out laparoscopically. Acceptance is increasing. After successful R0 resection, the rule for stage III patients is: adjuvant therapy is indicated regardless of age. Regimens containing oxaliplatin should be used. If there are contraindications for oxaliplatin, then fluoropyrimidine monotherapy is indicated, with oral fluoropyrimidines (capecitabine) being given precedence over infusional schemes. The use of 5-FU bolus regimens is regarded as obsolete. For stage II, the following applies: If an adjuvant chemotherapy is planned in these patients on the basis of the QUASAR data, then fluoropyrimidine monotherapy (e. g. capecitabine) can be given. Since patients whose tumours show a high frequency of microsatellite instability (MSI) do not benefit from a fluoropyrimidine monotherapy, the MSI status should be determined before choosing therapy. PMID:19546595

  11. Photodynamic therapy for the prevention of restenosis after angioplasty

    NASA Astrophysics Data System (ADS)

    Asahara, Takayuki; Usui, Mikio; Amemiya, Takashi; Oike, Yasuhisa; Shiraishi, Hiromori; Miyagi, Manabu; Nakajima, Hitoshi; Kato, Tomitsugu; Naito, Yuichi; Ibukiyama, Chiharu

    1993-06-01

    The purpose of this study was to evaluate whether photodynamic therapy (PDT) can destroy the proliferating smooth muscle cells and therefore suppress the occurrence of restenosis after angioplasty. PDT following administration of hematoporphyrin derivatives (HpD) 24 hours before irradiation was performed on 30 rabbits immediately (0D), 3 days (3D), 1 week (1W) and 2 weeks (2W) after balloon injury. HpD accumulation of each group was investigated simultaneously. Irradiation of 27 J/10 mm2 from an Hg-Xe flash lamp light transmitted through an 800 micrometers quartz fiber with a diffusing tip was used. All rabbits were sacrificed 4 weeks after balloon injury. The results were expressed in terms of intima:media thickness ratio at the site of fiber contact (I/M) and intima:media area ratio of the cross section (IA/MA). Inhibition of intimal thickening evaluated on the basis of the I/M ratio was recognized in the 3D-, 1W-, and 2W-PDT group. The most effective photoradiation was at the 1W-PDT (I/M equals 0.78 +/- 0.67), but in 2W-PDT intimal necrosis resulting in a small amount of thickness was observed with less media necrosis. ThreeD and 0D PDT effects reduced with media necrosis. We conclude that PDT after angioplasty would be an ideal preventional therapy of restenosis.

  12. Cell Death Pathways in Photodynamic Therapy of Cancer

    PubMed Central

    Mroz, Pawel; Yaroslavsky, Anastasia; Kharkwal, Gitika B; Hamblin, Michael R.

    2011-01-01

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT. PMID:23914299

  13. Photodynamic therapy for pancreatic and biliary tract carcinoma

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.

    2009-02-01

    Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

  14. Strategies to potentiate immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2015-03-01

    Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT a great potential to become more widely used. Although the stimulation of tumorspecific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. Other promising approaches involve depleting regulatory T-cells and epigenetic reversal agents. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.

  15. Phytotherapeutic and naturopathic adjuvant therapies in otorhinolaryngology.

    PubMed

    Ciuman, Raphael Richard

    2012-02-01

    Phytotherapeutic pharmaceuticals and herbal medicinal products with its roots in classical phytotherapeutic medicine have a well-established role in otolaryngological therapy, especially for diseases of the upper airways and acute and chronic infections. A thorough selection and application could mean huge benefit for the patient, in particular in cases with contraindications, chemo- and antibiotic resistance or patient request. Besides, it might spare other medications. Phytotherapeutic pharmaceuticals must fulfil the same criteria of quality, effectiveness and harmlessness of evidence-based medicine like chemical pharmaceuticals, although they are often prescribed due to its well established or traditional based use. This review focuses on phytotherapeutic therapies well established within the European Community for otolaryngologic disease patterns by referring to clinical studies or meta-analysis. PMID:21922427

  16. Photodynamic therapy of non-melanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Ikram, M.; Khan, R. U.; Firdous, S.; Atif, M.; Nawaz, M.

    2011-02-01

    In this prospective study duly approved from Institutional Ethics Review Committee for research in medicine, PAEC General Hospital Islamabad, Pakistan, we investigate the efficacy, safety and tolerability along with cosmetic outcome of topical 5-aminolaevulinic acid photodynamic therapy for superficial nonmelanoma skin cancers (NMSCs) and their precursors. Patients with Histological diagnosis of NMSCs and their precursors were assessed for PDT, after photographic documentation of the lesions and written consent, underwent two (2) sessions of PDT in one month (4 weeks) according to standard protocol. A freshly prepared 20% 5-ALA in Unguentum base was applied under occlusive dressing for 4-6 h as Drug Light Interval (DLI) and irradiated with light of 630 nm wavelength from a diode laser at standard dose of 90 J/cm2. Approximately 11% patients reported pain during treatment which was managed in different simple ways. In our study we regularly followed up the patients for gross as well as histopathological response and recurrence free periods during median follow-up of 24 months. Regarding Basal cell carcinomas complete response was observed in 86.2% (25/29), partial response in 10.3% (3/29) and recurrence during first year in 3.5% (1/29) lesions. All the lesions which showed partial response or recurrence were nBCCs. Regarding Actinic Keratosis complete response was observed in 95.3% (20/21), partial response in 4.7% (1/21) while Bowen's disease showed 100% (2/2) results. 81.8% (9/11) Squamous Cell Carcinomas showed complete, 9% (1/11) partial response and 9% (1/11) presented with recurrence after 3 months. We observed excellent and good cosmetic results along with tumor clearance in our study. Treatment sessions were well tolerated with high level of patient's satisfaction and only minor side effects of pain during treatment sessions and inflammatory changes post photodynamic therapy were observed. We concluded that 5-ALA PDT is an effective and safe emerging treatment modality for management of superficial non-melanoma skin cancers and their precursors with better cosmetic outcome and minor side effects.

  17. Photodynamic therapy as a treatment for esophageal squamous cell carcinoma in a dog.

    PubMed

    Jacobs, T M; Rosen, G M

    2000-01-01

    Intrathoracic esophageal squamous cell carcinoma was diagnosed by endoscopy in an 11-year-old, castrated male Labrador retriever with signs of regurgitation and weight loss. Photodynamic therapy with photofrin was administered three times under endoscopic guidance over a two-month period. A partial response to photodynamic therapy was supported by a reduction in tumor size (noted on serial endoscopic examinations) and by a return to oral alimentation. The dog was euthanized due to recurrent regurgitation and aspiration pneumonia nine months after the onset of therapy. Necropsy revealed marked local invasiveness and regional lymph node metastasis of the esophageal squamous cell carcinoma in addition to pneumonia. The application of photodynamic therapy in the treatment of canine esophageal squamous cell carcinoma is discussed and compared with the human literature. PMID:10825099

  18. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis

    NASA Astrophysics Data System (ADS)

    Fateye, B.; He, C.; Chen, B.

    2009-06-01

    Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

  19. Core – shell upconversion nanoparticle – semiconductor heterostructures for photodynamic therapy

    PubMed Central

    Dou, Qing Qing; Rengaramchandran, Adith; Selvan, Subramanian Tamil; Paulmurugan, Ramasamy; Zhang, Yong

    2015-01-01

    Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980?nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980?nm NIR light. PMID:25652742

  20. Measurement of photodynamic therapy drug concentrations in a tissue

    SciTech Connect

    Mourant, J.; Biglo, I.; Johnson, T.

    1996-09-01

    This is the final report of a one-year laboratory-directed research and development project at the Los Alamos National Laboratory (LANL). Photodynamic therapy (PDT) is an experimental treatment modality for cancer in which a photoactive molecule with an affinity for tumors in administered to the patient, then excited by light. Photoactivation creates singlet oxygen consequently killing the tissue. Knowledge of the concentration of the photoactive compound in the tissue is necessary for proper light dosimetry during PDT. Presently, the control of light application is problematic. If too much light is applied, damage to the surrounding tissue will occur. If insufficient light is applied, the targeted tissue volume will remain viable. The ideal implementation of PDT would use a feedback system for light delivery that incorporates the optical properties of the tissue and knowledge of the concentration of the photoactive compound. This project sought to develop a method for measuring photosensitizer concentrations in tissue phantoms that will lead to a noninvasive, endoscopically compatible, in vivo method of measuring PST drug concentrations.

  1. Fluorescence guided evaluation of photodynamic therapy as acne treatment

    NASA Astrophysics Data System (ADS)

    Ericson, Marica B.; Horfelt, Camilla; Cheng, Elaine; Larsson, Frida; Larko, Olle; Wennberg, Ann-Marie

    2005-08-01

    Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

  2. Targeting Epigenetic Processes in Photodynamic Therapy-Induced Anticancer Immunity

    PubMed Central

    Wachowska, Malgorzata; Muchowicz, Angelika; Golab, Jakub

    2015-01-01

    Photodynamic therapy (PDT) of cancer is an approved therapeutic procedure that generates oxidative stress leading to cell death of tumor and stromal cells. Cell death resulting from oxidative damage to intracellular components leads to the release of damage-associated molecular patterns (DAMPs) that trigger robust inflammatory response and creates local conditions for effective sampling of tumor-associated antigens (TAA) by antigen-presenting cells. The latter can trigger development of TAA-specific adaptive immune response. However, due to a number of mechanisms, including epigenetic regulation of TAA expression, tumor cells evade immune recognition. Therefore, numerous approaches are being developed to combine PDT with immunotherapies to allow development of systemic immunity. In this review, we describe immunoregulatory mechanisms of epigenetic treatments that were shown to restore the expression of epigenetically silenced or down-regulated major histocompatibility complex molecules as well as TAA. We also discuss the results of our recent studies showing that epigenetic treatments based on administration of methyltransferase inhibitors in combination with PDT can release effective mechanisms leading to development of antitumor immunity and potentiated antitumor effects. PMID:26284197

  3. Synthesis of folate receptor-targeted photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fang, Yanyan; Wang, Xiaopu; Zou, Qianli; Zhao, Yuxia; Wu, Feipeng

    2014-11-01

    A series of amphiphilic benzylidene cycloalkanes ketone photosensitizers C1-C4 with or without folate receptor-targeted agent were designed and synthesized. Their photophysical properties and in vitro photodynamic therapy (PDT) effects were studied. The results showed that all compounds exhibited appropriate lipid-water partition coefficients and high reactive oxygen yields. The introduction of the folate receptor-targeted agent had no obvious influence on the basic photophysical & photochemical properties of C2 and C4 compared to those of their corresponding prototype compounds (C1 and C3). In vitro studies were carried out using MCF-7 cells (FR+), Hela cells (FR+) and A549 cells (FR-), which represented different levels of folate receptor (FR) expression. All of C1-C4 showed low dark toxicity and superior PDT effects compared with the clinical drug PSD-007 (a mixture of porphyrins). What's more, folate receptor-targeted photosensitizers (C2 and C4) achieved higher accumulation and more excellent PDT effects in MCF-7 cells (FR+) and Hela cells (FR+) than photosensitizers (C1 and C3) without folate receptor-targeted agent and PSD-007. The photocytotoxicity of these photosensitizers showed no obvious differences in A549 cells (FR-).

  4. Photodynamic therapy in thoracic oncology: a single institution experience

    NASA Astrophysics Data System (ADS)

    Luketich, James D.; Fernando, Hiran C.; Christie, Neil A.; Litle, Virginia R.; Ferson, Peter F.; Buenaventura, Percival O.

    2001-04-01

    We have performed 800 photodynamic therapy (PDT) treatments in over 300 patients at the University of Pittsburgh since 1996. Over 150 patients have undergone PDT for palliation of dysphagia for esophageal cancer. Of the first 77 dysphagia improved in 90.8% with a mean dysphagia-free interval of 80 days. An expandable metal stent was required for extrinsic compression in 19 patients. We have treated 14 high-risk patients with early esophageal cancer or Barrett's high-grade dysplasia for curative intent. At a median follow-up of 12.8 months eight remain free of cancer. Over 100 patients have undergone PDT for lung cancer. Sixty-two patients received 77 courses for palliation. Thirty-five patients were treated for non-massive hemoptysis with resolution in 90%. Forty-four patients were treated for dyspnea with improvement in 59%. A subset of seven high-risk patients with early lung cancer were treated with curative intent. A complete response was seen in 7/10 lesions at a mean follow-up of 30 months. PDT offers good palliation for both advanced esophageal and lung cancer. The role of PDT for curative intent needs further investigation in protocol settings. In our preliminary experience we have treated a small number of non-surgical, high-risk patients with a reasonable success rate.

  5. Monte Carlo modelling of daylight activated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Campbell, C. L.; Wood, K.; Valentine, R. M.; Brown, C. T. A.; Moseley, H.

    2015-05-01

    The treatment of superficial skin lesions via daylight activated photodynamic therapy (PDT) has been explored theoretically with three dimensional (3D) Monte Carlo radiation transfer simulations. For similar parameters and conditions, daylight activated PDT was compared to conventional PDT using a commercially available light source. Under reasonable assumptions for the optical properties of the tissue, protoporphyrin IX (PpIX) concentration and a treatment dose of 75 J cm-2, it was found that during a clear summer day an effective treatment depth of over 2 mm can be achieved after 30 min of daylight illumination at a latitude of 56 degrees North. The same light dose would require 2.5 h of daylight illumination during an overcast summer day where a treatment depth of about 2 mm can be achieved. For conventional PDT the developed model suggests that 15 min of illumination is required to deliver a light dose of 75 J cm-2, which would result in an effective treatment depth of about 3 mm. The model developed here allows for the determination of photo-toxicity in skin tissue as a function of depth for different weather conditions as well as for conventional light sources. Our theoretical investigation supports clinical studies and shows that daylight activated PDT has the potential for treating superficial skin lesions during different weather conditions.

  6. [Indications for photodynamic therapy in age-related macular degeneration].

    PubMed

    Soubrane, G; Kuhn, D; Coscas, G

    2004-01-01

    Exudative age-related macular degeneration (ARMD) is now benefitting from new therapeutic approaches. Three international randomized clinical trials have demonstrated the efficacy of photodynamic therapy (PDT) in stabilizing visual acuity at 2 years. PDT is based on the activation of a photosensitizer with an adapted wavelength. In age-related macular degeneration, the photosensitizer used is verteporfin (Visudyne), which accumulates preferentially in choroidal new vessels. Functional results are obtained on the basis of a strict classification based on fluorescein angiography examining the type of the new vessels responsible for exudative ARMD. Thus, subfoveal lesions, either predominantly classic (>50%) or occult only, are the indication for PDT. Classic CNVs where laser photocoagulation thermal burns extend into the foveola may be an extrapolation of the indication for PDT. In addition, fluorescein angiography is essential for considering retreatment, usually necessary. Demonstrated growth and the persistence of leakage from the CNV is an absolute indication for a new session of PDT. A number of features still require assessment in order to define the responder group more accurately and to refine and possibly simplify the indications for retreatment. PMID:14968084

  7. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  8. An update on photodynamic therapies in the treatment of onychomycosis.

    PubMed

    Simmons, B J; Griffith, R D; Falto-Aizpurua, L A; Nouri, K

    2015-07-01

    Onychomycosis is a common fungal infection of the nails that is increasing in prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a therapeutic challenge that can lead to significant reductions in quality of life leading to both physical and psychological consequences. Current treatment modalities are difficult to implement due to the poor penetration of topical treatments to the nail bed, the slow growing nature of nails and the need for prolonged use of topical and/or oral medications. Standard of care medications have cure rates of 63-76% that leads to a high propensity of treatment failures and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and aminolevulinic acid (ALA) have been used as photosensitizers with approximately 630 nm light. These modalities are combined with pre-treatment of urea and/or microabrasion for better penetration. PDT treatments are well tolerated with only mild transient pain, burning and erythema. In addition, significant cure rates for patients who have contraindications to oral medications or failed standard medications can be obtained. With further enhancements in photosensitizer permeability, decreased pre-treatment and photosensitizer incubation times, PDT can be a more efficient and cost-effective in office based treatment for onychomycosis. However, more large-scale randomized control clinical trials are needed to access the efficacy of PDT treatments. PMID:25589056

  9. Towards recombinant antibody-fragment targeted photodynamic therapy.

    PubMed

    Milgrom, Lionel R

    2008-01-01

    For the treatment of tumours and other proliferative conditions, widespread uptake of photodynamic therapy (PDT) has to some extent been hindered by its inability to target specifically photosensitisers (PSs) to localised lesions in the body. PSs may be deposited in the skin, leading to painful and disfiguring photosensitivity, sometimes for weeks after initial treatment. Targeting PSs specifically could not only avoid such side-effects, it could greatly improve PDT's therapeutic margin. This review describes photoimmunoconjugates (PICs) produced via successful combination of PSs with recombinant monoclonal antibody fragments (sc-Fvs). PICs can not only target specifically and destroy tumour cells in vitro and in vivo, but counter-intuitively, it is possible to conjugate many more PSs to an sc-Fv than to the much larger parent monoclonal antibody. The general utility of PICs is demonstrated by significant improvements to the potency and selectivity of already existing PSs. Furthermore, critical features of sc-Fvs are discussed that enable them to make effective PICs. This has implications for the future engineering of scFv carriers for PDT, in order to control the number and function of the PSs that can be coupled. PMID:18853576

  10. Photodynamic Therapy: One Step Ahead with Self-Assembled Nanoparticles

    PubMed Central

    Avci, Pinar; Erdem, S. Sibel; Hamblin, Michael R.

    2014-01-01

    Photodynamic therapy (PDT) is a promising treatment modality for cancer with possible advantages over current treatment alternatives. It involves combination of light and a photosensitizer (PS), which is activated by absorption of specific wavelength light and creates local tissue damage through generation of reactive oxygen species (ROS) that induce a cascade of cellular and molecular events. However, as of today, PDT is still in need of improvement and nanotechnology may play a role. PDT frequently employs PS with molecular structures that are highly hydrophobic, water insoluble and prone to aggregation. Aggregation of PS leads to reduced ROS generation and thus lowers the PDT activity. Some PS such as 5-aminolevulinic acid (ALA) cannot penetrate through the stratum corneum of the skin and systemic administration is not an option due to frequently encountered side effects. Therefore PS are often encapsulated or conjugated in/on nano-drug delivery vehicles to allow them to be better taken up by cells and to more selectively deliver them to tumors or other target tissues. Several nano-drug delivery vehicles including liposomes, fullerosomes and nanocells have been tested and reviewed. Here we cover non-liposomal self-assembled nanoparticles consisting of polymeric micelles including block co-polymers, polymeric micelles, dendrimers and porphysomes. PMID:25580097

  11. Photodynamic therapy for melanoma: efficacy and immunologic effects

    NASA Astrophysics Data System (ADS)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  12. Photodynamic Therapy and the Development of Metal-Based Photosensitisers

    PubMed Central

    Josefsen, Leanne B.; Boyle, Ross W.

    2008-01-01

    Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT. PMID:18815617

  13. Viability for the conjugate use of electrosurgery and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rego-Filho, Francisco G.; Vieira, Edson; Kurachi, Cristina; Bagnato, Vanderlei S.; de Araujo, Maria T.

    2011-07-01

    Photodynamic Therapy (PDT) is a technique for destroying tumor cells with little harm to surrounding healthy tissue. However, the light wavelength has limited penetration in the tissue, making the association of a surgical procedure needed for larger lesions. Electrosurgery (ES) is a recommended excision technique, but the optical properties of the tissue damaged by ES and its influence on PDT procedure are unknown. Twelve rats (Wistar) composed the animal model of four groups (ES, PDT, ES+PS+Light, PS+ES+Light), evaluating different orders of conjugation via fluorescence, imaging and necrosis depth. First histopathological analysis has shown a highly modified surface of tissue (integral structure loss and dehydration shrinkage), protein denaturation, accompanied by bleeding and inflammatory damage. Fluorescence imaging showed strong scattering of light at the surface of modified tissue, which may cause higher losses of light on the surface. Fluorescence spectra showed different photosensitizer emissions for distinct operation modes. The different tissue composition can also induce changes on absorption and scattering properties, influencing the light penetration. The study showed significant necrosis formation beyond the limits of electrosurgery damage, making possible the conjugate use of ES and PDT.

  14. Core - shell upconversion nanoparticle - semiconductor heterostructures for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Dou, Qing Qing; Rengaramchandran, Adith; Selvan, Subramanian Tamil; Paulmurugan, Ramasamy; Zhang, Yong

    2015-02-01

    Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

  15. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  16. Predictive analysis of photodynamic therapy applied to esophagus cancer

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2008-04-01

    The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

  17. Topical photodynamic therapy for nevus sebaceous on the face.

    PubMed

    In, Sung-Il; Lee, Jae Yeol; Kim, You Chan

    2010-01-01

    Recently, topical photodynamic therapy (PDT) has been tried to treat sebaceous gland disorders. However, only one case of nevus sebaceous treated with PDT has been reported. Our aim was to investigate the outcomes of PDT on nevus sebaceus on the face. A total of 12 patients were treated with topical 20% ALA or methyl aminolevulinate (MAL) after CO(2) laser ablasion. The lesions were irradiated with light emitting diodes (LED) device. The regimen was delivered repeatedly at 1 to 4 week intervals to each patient. Clinical improvement was visually assessed at 1 month after treatment by the lesional responses; No response was defined as less than 25%, mild improvement as 25-50%, moderate improvement as 51-75% and marked improvement as more than 75% decrease of lesional volume. All 12 patients showed mild (3 patients, 25%), moderate (7 patients, 58%), and marked (2 patients, 17%) improvement of the lesions. However, 2 patients showed partial recurrences after completion of treatment. There was no significant side effect.These results suggest that topical PDT may be considered as an effective alternative treatment modality of nevus sebaceous on the face. PMID:20709645

  18. Absence of bacterial resistance following repeat exposure to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

    2009-06-01

    The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were <100% so that surviving colonies could be passaged for subsequent exposures. With each repeat, kills were compared to those using non-exposed cultures of the same strain. Oxacillin resistance was induced in S. aureus using a disc diffusion method. For each experiment, "virgin" and "repeat" cultures were exposed to methylene blue at 0.01% w/v and illuminated with an energy dose of 20.6 J/cm2. No significant difference in killing of E. coli (repeat vs. virgin culture) was observed through 11 repeat exposures. Similar results were seen using MSSA and MRSA, wherein kill rate did not significantly differ from control over 25 repeat exposures. In contrast, complete oxacillin resistance could be generated in S. aureus over a limited number of exposures. PDT is effective in the eradication of pathogens including antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

  19. Four-year clinical experience in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Vorozhtsov, Georgy N.; Mironov, Andrei F.; Markichev, Nikolai A.; Riabov, Michail V.

    1996-12-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of skin, breasts, tongue, oral mucose, lower lip, larynx, stomach, bladder, rectum and other locations has been made. During 1992 - 1996 867 tumoral foci in 222 patients have been treated with PDT. All patients were previously treated with conventional techniques or they were not treated due to contraindications either because of severe accompanying diseases or because of old age. A part of the patients had PDT because of recurrences or intradermal metastases in 1 - 2 years after surgical, radial or combined treatment. Up to now we have follow-up control data within 2 months and 4 years. Positive effect of PDT was seen in 93.7% of patients including complete regression of tumors in 64.9% and partial in 28.8%. Currently this new perspective technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

  20. Five years experience of photodynamic therapy with new chlorin photosensitizer

    NASA Astrophysics Data System (ADS)

    Privalov, Valery A.; Lappa, Alexander V.; Kochneva, Elena V.

    2005-08-01

    Clinical results of photodynamic therapy (PDT) with a novel natural second generation chlorin-type photosensitizer "Radachlorin", mainly consisting of sodium chlorine e6, are presented. This sensitizer possesses a number of advantages over sensitizers of hematoporphyrin and phthalocyanine types. In particular, Radachlorin is excreted from organism much faster (in 1-2 days), as a result the problem of patient light hypersensitivity for a few months is non-actual for Radachlorin. As light source there was used a 662 nm diode laser specially designed for PDT with Radachlorin. The 5 year clinical results of PDT application to 89 patients with different malignant tumors are summarized and analysed. It is shown in particular that PDT with Radachlorin is a radical high efficient method for treatment of basal cell carcinoma of skin. At intravenous introduction in drug dose 0.5 mg/kg with light fluence 300-350 J/cm2 or in dose 1 mg/kg with fluence 200-250 J/cm2 the method gives full recovery in almost 100% cases with excellent cosmetic effect. The method was successfully combined with surgical operations, laser ablations, radio- and chemotherapy. Preoperative and intraoperative PDT favors improvement of results in complex treatment of malignant tumors. The method has a potential as palliative measure; in a number of incurable cases it allowed us to achieve recanalization of obturated hollow organs, eliminate the inflammatory complications, and as a result to improve life quality.

  1. Photodynamic therapy of cancer: five-year clinical experience

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Vorozhtsov, Georgy N.; Mironov, Andrei F.; Beshleul, Stanislav E.; Markitchev, Nikolai A.; Riabov, Michail V.

    1997-12-01

    The results of application of photodynamic therapy (PDT) for treatment of malignant tumors of skin, breasts, tongue, oral mucose, lower lip, larynx, stomach, bladder, rectum and other localizations were assessed. In 1992 - 1997 more than 1200 tumoral foci in 288 patients have been treated with PDT. Most of the patients have been taken for PDT for tumoral recurrences or intradermal metastases after surgery, gamma- therapy or combined treatment. A certain number of patients had not been treated before due to severe accompanying diseases or old age. Russian photosensitizers Photoheme in dosage 1.0 - 5.0 mg/kg body weight, and Photosense in dosage 0.5 - 1.5 mg/kg body weight were used. Laser irradiation was performed using Coherent 'Innova-200' and Russian laser devices: copper vapor-pumped dye laser (wavelength 630 nm, output power -- 5 W), gold-vapor lasers (wavelength 628 nm, output power -- 2 W), solid-state laser (wavelength 670 nm, output power -- 2 W). In several cases non-laser light emitting devices have been employed. Up to date we possess the follow-up data in term from 2 months to 5 years. Therapeutic effect took place in 94.4% of the cases, including complete tumor resorption in 56.2% and partial resorption in 38.2% of the cases. The results of PDT application for treating malignant tumors allow one to estimate PDT as an adequate technique and in some tumor localizations PDT might become a method of choice. This new promising technique of cancer treatment is successfully applied in Russia. New photosensitizers and sources of light for PDT and fluorescent diagnostics are being developed.

  2. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  3. Ratiometric Biosensor for Aggregation-Induced Emission-Guided Precise Photodynamic Therapy.

    PubMed

    Han, Kai; Wang, Shi-Bo; Lei, Qi; Zhu, Jing-Yi; Zhang, Xian-Zheng

    2015-10-27

    Photodynamic therapy faces the barrier of choosing the appropriate irradiation region and time. In this paper, a matrix metalloproteinase-2 (MMP-2) responsive ratiometric biosensor was designed and synthesized for aggregation-induced emission (AIE)-guided precise photodynamic therapy. It was found that the biosensor presented the MMP-2 responsive AIE behavior. Most importantly, it could accurately differentiate the tumor cells from the healthy cells by the fluorescence ratio between freed tetraphenylethylene and protoporphyrin IX (PpIX, internal reference). In vivo study demonstrated that the biosensor could preferentially accumulate in the tumor tissue with a relative long blood retention time. Note that the intrinsic fluorescence of PpIX and MMP-2-triggered AIE fluorescence provided a real-time feedback which guided precise photodynamic therapy in vivo efficiently. This strategy demonstrated here opens a window in the precise medicine, especially for phototherapy. PMID:26348984

  4. Retinal Capillary Hemangioma Treated with Verteporfin Photodynamic Therapy and Intravitreal Triamcinolone Acetonide

    PubMed Central

    Suh, Shin Cho; Jin, Sun Young; Kim, Chul Gu; Kim, Jong Woo

    2007-01-01

    Purpose To report a case of retinal capillary hemangioma treated with verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide. Methods A 15-year-old female presented with metamorphopsia in the left eye for 7 days. Examination showed peripheral endophytic retinal capillary hemangioma, macular edema, and a best-corrected visual acuity of 20/50. The hemangioma and macular edema were treated with verteporfin photodynamic therapy and intravitreal triamcinolone acetonide. Results After 5 months of follow-up, involution of the hemangioma, reduction of macular edema, decrease of the feeder and draining vessel diameter, and improvement of best-corrected visual acuity to 20/25 was seen. Conclusions This verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide appeared to cause involution of the hemangioma with reduction in macular edema and improvement in visual acuity. PMID:17804927

  5. Contrast enhanced-magnetic resonance imaging as a surrogate to map verteporfin delivery in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Bryant, Amber; Gunn, Jason R.; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2013-12-01

    The use of in vivo contrast-enhanced magnetic resonance (MR) imaging as a surrogate for photosensitizer (verteporfin) dosimetry in photodynamic therapy of pancreas cancer is demonstrated by correlating MR contrast uptake to ex vivo fluorescence images on excised tissue. An orthotopic pancreatic xenograft mouse model was used for the study. A strong correlation (r=0.57) was found for bulk intensity measurements of T1-weighted gadolinium enhancement and verteporfin fluorescence in the tumor region of interest. The use of contrast-enhanced MR imaging shows promise as a method for treatment planning and photosensitizer dosimetry in human photodynamic therapy (PDT) of pancreas cancer.

  6. Photodynamic therapy: a new antimicrobial approach to infectious disease?

    PubMed Central

    Hasan, Tayyaba

    2011-01-01

    Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(?) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(?) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naïve strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin. PMID:15122361

  7. Photodynamic antimicrobial therapy of curcumin in biofilms and carious dentine.

    PubMed

    Araújo, N C; Fontana, C R; Bagnato, V S; Gerbi, M E M

    2014-03-01

    Photodynamic therapy (PDT) is a technique that involves the activation of photosensitizers by light in the presence of oxygen, resulting in the production of reactive radicals that are capable of inducing cell death. The present study evaluated the susceptibility of Streptococcus mutans and Lactobacillus acidophilus to PDT grown as multi-species in the biofilm phase versus in dentine carious lesions. A brain-heart infusion culture medium supplemented with 1% glucose, 2% sucrose, and 1% young primary culture of L. acidophilus 10(8) CFU/mL and S. mutans 10(8) CFU/mL was used to develop multi-species biofilms and to induce caries on human dentine slabs. Five different concentrations of curcumin (0.75, 1.5, 3.0, 4.0, and 5.0 g/L) were used associated with 5.7 J/cm(2) light emission diode. Four different groups were analyzed L-D- (control group), L-D+ (drug group), L+D- (light group), and L+D+ (PDT group). ANOVA/Tukey's tests were conducted to compare groups. A significant reduction (p <0.05) in cell viability was observed in the biofilm phase following photosensitization with all curcumin concentrations tested. To achieve significant bacterial reduction (p <0.05) in carious dentine, it was necessary to utilize 5.0 g/L of curcumin in association with blue light. No significant reduction was found for L-D+, supporting the absence of the drug's dark toxicity. S. mutans and L. acidophilus were susceptible to curcumin in the presence of blue light. However, due to light penetration and drug diffusion difficulties, these microorganisms within dentine carious lesions were less affected than they were in the biofilm phase. PMID:23793414

  8. Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

    2005-01-01

    Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

  9. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  10. Pentamethylpyrromethene boron difluoride complexes in human ovarian cancer photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Morgan, Lee R.; Chaudhuri, Aulena; Gillen, Laura E.; Boyer, Joseph H.; Wolford, Lionel T.

    1990-07-01

    Quasiaromatic heterocycles (QAM) such as substituted 1 , 3 , 5 , 7 , 8-pentamethylpyrromethene boron difluorides (PMP-BF2) and - (dimethoxyphosphinylmethyl, methyl) bimane have been evaluated for their abilities to produce cellular toxicities when used in photodynamic therapy (PDT) for ovarian cancer. The most active QAH tested to date has been the disodiuxn salt of PMP-2,6-disulfonate--BF2 (PMPDS-BF2). Human ovarian cancer cells from fifteen different patients have been grown in culture. Cells were obtained from biopsy material and grown in RPMI medium with 10% FBA plus penicillin and streptomycin. Cells were harvested and as single cell suspensions exposed to PMP-BF2 complexes or bimanes in concentrations of 0.004-0.4 ug/106 cells/ml of medium. Initially the cells were exposed to the chemicals for 30 minutes in a 5% CO2 incubator (37°C) with gentle shaking. The cells were washed with plain RPMI medium, then resuspended in the enriched RPMI medium and exposed to a sunlamp for 10-20 minutes. Cells were then allowed to grow in an soft agar culture media at 37°C (5% C02) for 14 days. When compared to controls (only light or only chemicals) there was 100% inhibition of all cellular growth for PMPDSBF2 at the 0.4 ug/mi concentrations. There was variations in concentrations of the chemical needed to produce 100% inhibition when the 15 different ovarian cancer cell specimens were compared at all concentrations. PMP-BF2 complexes are characterized by extremely high extinction coefficients, superior laser activity and little if any triplet-triplet absorption. The biamanes share these properties however are less active in ovarian cancer cell The lasing properties of PMP-BF2, and bimanes will be compared to their PDT effectiveness.

  11. Canine treatment with SnET2 for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Frazier, Donita L.; Milligan, Andrew J.; Vo-Dinh, Tuan; Morgan, Alan R.; Overholt, Bergein F.

    1990-07-01

    Photodynamic therapy is a treatment technique that utilizes the photoactived species of a drug to destroy tumor tissue. To be successful, the drug must localize in tumor tissue preferentially over normal tissue and must be activated by light of a specific wavelength. Currently the only drug to be approved for clinical use is Heinatoporphyrin Derivative (HpD) although a series of new drugs are being developed for use in the near future. One of the drugs belongs to a class called purpurins which display absorp-' tions between 630-711 nm. Along with several other investigators, we are currently exploring the characteristics of a specific purpurin (SnET2) in normal and tumorous canine tissue. The use of this compound has demonstrated increased tumor control rates in spontaneous dog tumors. Preliminary pharmacokinetic studies have been performed on 6 normal beagle dogs. SnET2 (2 mg/kg) was injected intravenously over 10 minutes and blood was collected at 5, 15, 30, 45 minutes and at 1, 2, 4, 8, 12 and 24 hours following administration for determination of drug concentration and calculation of pharinacokinetic parameters. Skin biopsies were collected at 1, 4, 8, 12 and 24 hours. Dogs were euthanized at 24 hours and tissues (liver, kidney muscle, esophagus, stomach, duodenum, jejunum, ileura, colon, adrenal gland, thyroid, heart, lung, urinary bladder, prostate, pancreas, eye, brain) were collected for drug raeasurement. Drug was shown to persist in liver and kidney for a prolonged period of time coiapared to other tissues. Knowledge of the pharmacokinetic properties of the drug will greatly add to the ability to treat patients with effective protocols.

  12. Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets

    NASA Astrophysics Data System (ADS)

    Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

    2014-09-01

    Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03753g

  13. Using antimicrobial adjuvant therapy in cancer treatment: a review

    PubMed Central

    2012-01-01

    Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial therapy is beneficial in cancer treatment. There could be several reasons for this effect, which include treating cancer associated bacteria and viruses, prophylaxis of post-chemotherapy infections due to immunosuppression, and antiproliferative effect of certain antimicrobials. Targeting cancer associated viruses and bacteria with antimicrobial agents is currently used for gastric, cervical, hematopoietic, liver and brain cancer. However this treatment is effective only in combination with conventional therapies. Antimicrobials can also have a direct antiproliferative and cytotoxic effect, and can cause apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming side effects of drugs commonly used in cancer treatment. Chemotherapy related bacteremia and neutropenia can be overcome by the appropriately timed use of antimicrobials. This review summarizes the data on the effects of antivirals and antibiotics on cancer treatment and describes their mechanisms. PMID:23164412

  14. Manual and rotary instrumentation ability to reduce Enterococcus faecalis associated with photodynamic therapy in deciduous molars.

    PubMed

    Pinheiro, Sérgio Luiz; Silva, Josianne Neres da; Gonçalves, Rafael Orro; Villalpando, Karina Teixeira

    2014-01-01

    This aim of this study was to assess the ability of manual or rotary instrumentation associated with photodynamic therapy (PDT) to reduce Enterococcus faecalis using three combinations of light/photosensitizers: toluidine blue O/laser, fuchsin/halogen light and fuchsin/LED. Twenty deciduous molars were selected and contaminated with Enterococcus faecalis (McFarland 0.5 scale). Working length determination was performed by visual method. The teeth were randomly divided into two groups: G1 (n=10): manual instrumentation (Kerr-type files) and G2 (n=10): rotary instrumentation (ProTaper system). The bacteria were collected three times using sterile paper cones compatible with the anatomic diameter of the root canal for 30 s before and after instrumentation and after PDT. The samples were diluted in peptone water, seeded on blood agar plates and incubated in an oven at 37 °C for colony-forming units counting. The decrease of E. faecalis counts after instrumentation and after PDT was compared using the Wilcoxon test, t-test and Kruskal Wallis test. A significant reduction of E. faecalis occurred after manual and rotary instrumentation and after PDT using the three combinations of light/photosensitizer (p<0.05). It may be concluded that both rotary and manual instrumentation reduced E. faecalis. Fuchsin with halogen light or LED irradiation and toluidine blue O with laser irradiation can be used to reduce E. faecalis in root canals of primary molars. PDT can be used as an adjuvant to conventional endodontic treatment. PMID:25590196

  15. Studies of photodynamic therapy: Investigation of physiological mechanisms and dosimetry

    NASA Astrophysics Data System (ADS)

    Woodhams, Josephine Helen

    Photodynamic therapy (PDT) is a treatment for a range of malignant and benign lesions using light activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen species (in particular singlet oxygen). Since the PDT cytotoxic effect depends on oxygen, monitoring of tissue oxygenation during PDT is important for understanding the basic physiological mechanisms and dosimetry of PDT. This thesis describes the use of non-invasive, optical techniques based on visible light reflectance spectroscopy for the measurement of oxy- to deoxyhaemoglobin ratio or haemoglobin oxygen saturation (HbSat). HbSat was monitored at tissue sites receiving different light dose during aluminium disulphonated phthalocyanine (AIS2PC) PDT. Results are presented on real time PDT-induced changes in HbSat in normal tissue (rat liver) and experimental tumours, and its correlation with the final biological effect under different light regimes, including fractionated light delivery. It was found to some extent that changes in HbSat could indicate whether the tissue would be necrotic after PDT and it was concluded that online physiological dosimetry is feasible for PDT. The evaluation of a new photosensitiser for PDT called palladium-bacteriopheophorbide (WST09) has been carried out in normal and tumour tissue in vivo. WST09 was found to exert a strong PDT effect but was active only shortly after administration. WST09 produced substantial necrosis in colonic tumours whilst only causing a small amount of damage to the normal colon under certain conditions indicating a degree of selectivity. Combination therapy with PDT for enhancing the extent of PDT-induced damage has been investigated in vivo by using the photochemical internalisation (PCI) technique and Type 1 mechanism enhanced phototoxicity with indole acetic acid (IAA). PCI of gelonin using AIS2PC PDT in vivo after systemic administration of gelonin was shown to enhance the effect of PDT in normal liver. The use of PDT and IAA did not result in a synergistic response.

  16. Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma.

    PubMed

    Bae, Byoung-chan; Yang, Su-Geun; Jeong, Seok; Lee, Don Haeng; Na, Kun; Kim, Joon Mee; Costamagna, Guido; Kozarek, Richard A; Isayama, Hiroyuki; Deviere, Jacques; Seo, Dong Wan; Nageshwar Reddy, D

    2014-10-01

    Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. PMID:25043500

  17. Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

    PubMed Central

    Chen, Rui; Zhang, Luzhong; Gao, Jian; Wu, Wei; Hu, Yong; Jiang, Xiqun

    2011-01-01

    Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource. PMID:21765637

  18. Phage Therapy and Photodynamic Therapy: Low Environmental Impact Approaches to Inactivate Microorganisms in Fish Farming Plants

    PubMed Central

    Almeida, Adelaide; Cunha, Ângela; Gomes, Newton C.M.; Alves, Eliana; Costa, Liliana; Faustino, Maria A.F.

    2009-01-01

    Owing to the increasing importance of aquaculture to compensate for the progressive worldwide reduction of natural fish and to the fact that several fish farming plants often suffer from heavy financial losses due to the development of infections caused by microbial pathogens, including multidrug resistant bacteria, more environmentally-friendly strategies to control fish infections are urgently needed to make the aquaculture industry more sustainable. The aim of this review is to briefly present the typical fish farming diseases and their threats and discuss the present state of chemotherapy to inactivate microorganisms in fish farming plants as well as to examine the new environmentally friendly approaches to control fish infection namely phage therapy and photodynamic antimicrobial therapy. PMID:19841715

  19. Photodynamic therapy suppresses tumor growth in an in vivo model of human hemangioma.

    PubMed

    Choi, Jaehoon; Kim, Woo Jung; Park, Sang Woo; Xu, Lianji; Kim, Sang-Hyon; Min, Hye Sook; Kwon, Geun-Yong; Cho, Chung-Hyun; Kim, Sukwha; Choi, Tae Hyun

    2014-01-01

    The authors investigated the efficacy of photodynamic therapy against infantile hemangioma using a hemangioma animal model. Eighty-three hemangioma specimens from five children were implanted into nude mice. The gross and volume changes of the implants were evaluated for up to 13 weeks. The histological change of the implant was evaluated at 5 weeks after transplantation. Photodynamic therapy was performed between 6 and 10 weeks after transplantation. The photosensitizer uptake of the implant was evaluated at 24 h after photosensitizer administration. The implant response was evaluated at 0, 12, and 24 h after light delivery. The change in ATF3 levels, a transcription factor induced under severe hypoxic conditions, was investigated immediately after treatment. The implant volume increased slowly during the first 4 weeks and then involuted. At 5 weeks after transplantation, plump endothelial cells formed tightly packed sinusoidal channels, and the endothelial cells were positive for CD31 and GLUT1 expression. At 24 h after photosensitizer administration, confocal analysis showed that the photosensitizer was present within CD31-positive cells. The implant volume was significantly decreased in the treated implants compared with the untreated implants (p < 0.0001). At 24 h after light delivery, most cells had collapsed. ATF3 expression increased gradually and then reached a maximum level at 4 h after treatment. Photodynamic therapy was effective in the treatment of infantile hemangioma. Apoptosis, a major mechanism of hemangioma destruction in the early phase, might be caused by ischemic injury as well as direct effects of photodynamic therapy. PMID:23784382

  20. A rationale for treating leg length discrepancy using photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Johnson, Crystal; Diab, Mohammed; Wilson, Brian C.; Burch, Shane

    2005-09-01

    This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1? was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized effects on bone development that may be applicable to other related skeletal deformities.

  1. Biomedical applications of nano-titania in theranostics and photodynamic therapy.

    PubMed

    Rehman, F U; Zhao, C; Jiang, H; Wang, X

    2015-12-15

    Titanium dioxide (TiO2) is one of the most abundantly used nanomaterials for human life. It is used in sunscreen, photovoltaic devices, biomedical applications and as a food additive and environmental scavenger. Nano-TiO2 in biomedical applications is well documented. It is used in endoprosthetic implants and early theranostics of neoplastic and non-neoplastic maladies as a photodynamic therapeutic agent and as vehicles in nano-drug delivery systems. Herein, we focus on the recent advancements and applications of nano-TiO2 in bio-nanotechnology, nanomedicine and photodynamic therapy (PDT). PMID:26442645

  2. Photodynamic Therapy as Novel Treatment for Halitosis in Adolescents: A Case Series Study

    PubMed Central

    Lopes, Rubia Garcia; de Santi, Maria Eugenia Simões Onofre; Franco, Bruno Edin; Deana, Alessandro Melo; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Ferrari, Raquel Agnelli Mesquita; Bussadori, Sandra Kalil

    2014-01-01

    Introduction: Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% of cases and systemic in 10% of cases. The foul odor is caused mainly by volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light with and without the combination of chemical agents has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by the photosensitizing dye. The aim of the present case series study was to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using a sulfide meter (Halimeter®). Methods: Five adolescents aged 14 to 16 years were evaluated using a sulfide meter before and one hour after photodynamic therapy, which involved the use of methylene blue 0.005% on the middle third and posterior thirds of the dorsum of the tongue and nine points of laser irradiation in the red band (660 nm) with an energy dose of 9 J, power output of 100 mW and 90-seconds exposure time. Results: A 31.8% reduction in the concentration of volatile sulfur compounds was found in the comparison of the initial and final readings. The statistically significant reduction (p = 0.0091) led to an absence of halitosis following treatment (mean: 58.2 ppb). Conclusion: Photodynamic therapy seems to be effective on reduction the concentration of volatile sulfur compounds.Considering the positive effects of photodynamic therapy in this case series, further studies involving microbiological analyses should be conducted to allow comparisons of the results. PMID:25653814

  3. Theoretical estimations of the area of destruction in brain tumors under photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bidnenko, Vadym N.; Sigal, Valeriy L.; Rozumenko, Vladimir D.

    2000-11-01

    It's proposed reaction-diffusion mathematical model for evaluating efficiency and destruction area of brains' rumor under photodynamic-laser therapy. The modeling is based on physical mechanism of tissue's effect by singlet oxygen, which display oxidizer's function. Kinetic description of process is proceeded from model of M.J.C. van Gemert, that was worked out diffusion's mechanism of triplet oxygen's spreading in tissue under photodynamic therapy. All calculations are carried out for red laser with wavelength 630nm and photofrin2, as photosensitizer, and for the second type of photo-physical reactions of such molecules. The space-time tissue dependencies of concentrations of possibility conditions of oxygen and photosensitizers are calculated. As was theoretical shown, effect of photodynamic destruction of tumor by singlet oxygen, particularly in brain, not depends from intensity of laser's irradiation, but is dictated by summation does, which is absorbed by tissue in all time of process. The hyperhypoxic's effects in tumor, that accompany of photodynamic therapy, strongly increases with decreases of light's attenuation coefficient in tissue medium.

  4. Own experience in treatment of patients with penile cancer using photodynamic therapy.

    PubMed

    Filonenko, Elena; Kaprin, Andrey; Alekseev, Boris; Urlova, Antonina

    2015-01-01

    Penile cancer is a rare pathology. For penile cancer surgical treatment, radiotherapy, chemotherapy, and combined modality treatment are available. Because of great importance of this organ for mental condition of patient, the development of organ-preserving methods allowing to minimize impact on patient's quality of life without compromising of oncological results is desirable. In the Center of Laser and Photodynamic diagnosis and treatment of tumors in P.A. Herzen Moscow Cancer Research Institute the methods of photodynamic therapy in patients with penile cancer have been developed. From 2011 to 2013 the treatment was conducted in 11 patients with precancer and cancer of penile. The average age was 56.6. According to morphological diagnosis photodynamic therapy (PDT) was performed using two methods. One method included topical application of agent for PDT and the second intravenous administration of photosensitizer. For topical application alasens was used and for intravenous injection we applied radachlorine. All patients had no complications. Complete regression was achieved in 9 patients, and partial regression in 2. Thus, the results showed that photodynamic therapy for penile cancer stage Tis-1N0M0 permits performing organ-preserving treatment with satisfactory oncological results and no impairment of patient's quality of life. PMID:25834812

  5. Own Experience in Treatment of Patients with Penile Cancer Using Photodynamic Therapy

    PubMed Central

    Filonenko, Elena; Kaprin, Andrey; Alekseev, Boris; Urlova, Antonina

    2015-01-01

    Penile cancer is a rare pathology. For penile cancer surgical treatment, radiotherapy, chemotherapy, and combined modality treatment are available. Because of great importance of this organ for mental condition of patient, the development of organ-preserving methods allowing to minimize impact on patient's quality of life without compromising of oncological results is desirable. In the Center of Laser and Photodynamic diagnosis and treatment of tumors in P.A. Herzen Moscow Cancer Research Institute the methods of photodynamic therapy in patients with penile cancer have been developed. From 2011 to 2013 the treatment was conducted in 11 patients with precancer and cancer of penile. The average age was 56.6. According to morphological diagnosis photodynamic therapy (PDT) was performed using two methods. One method included topical application of agent for PDT and the second intravenous administration of photosensitizer. For topical application alasens was used and for intravenous injection we applied radachlorine. All patients had no complications. Complete regression was achieved in 9 patients, and partial regression in 2. Thus, the results showed that photodynamic therapy for penile cancer stage Tis-1N0M0 permits performing organ-preserving treatment with satisfactory oncological results and no impairment of patient's quality of life. PMID:25834812

  6. Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets.

    PubMed

    Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

    2014-10-01

    Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. PMID:25126952

  7. [The role of intraoperative photodynamic therapy in complex treatment of cerebral metastases].

    PubMed

    Kurzhupov, M I; Zaitsev, A M; Loshakov, V A; Filonenko, E V

    2010-01-01

    Cerebral metastases are the most common brain tumors in adults and are characterized by poor prognosis. Despite application of modern methods of treatment (microsurgery, radiation therapy, chemotherapy) survival rates of these patients remain low. This fact triggers development of new therapeutic options which are able to increase recurrence-free period and consequently overall survival. The article contains review of literature dealing with photodynamic therapy which is a newly introduced technique for treatment of cerebral metastases. PMID:21254577

  8. [Endotoxin adsortion as adjuvant therapy in gram negative severe sepsis].

    PubMed

    Candel, F J; Martínez-Sagasti, F; Borges, M; Maseda, E; Herrera-Gutiérrez, M; Garnacho-Montero, J; Maynar, F J; Zaragoza, R; Mensa, J; Azanza, J R

    2010-09-01

    The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gram negative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge. PMID:20844841

  9. Two-photon photodynamic therapy and its potential application to age related macular degenerations

    NASA Astrophysics Data System (ADS)

    Karotki, Aliaksandr; Khurana, Mamta; Bisland, Stuart K.; Moriyama, Eduardo H.; Simpson, E. Rand; Campbell, Melanie C. W.; Collins, Hazel; Anderson, Harry L.; Cramb, David T.; Wilson, Brian C.

    2007-02-01

    Photodynamic therapy (PDT) using verteporfin is widely used for treatment of age related macular degeneration (AMD). Due to non-perfect selectivity of the drug accumulation in the neovasculature some collateral damage to healthy tissue arises during the treatment. Damage to healthy structures in the eye is always a concern because of a high probability of reducing visual acuity. Two-photon (2-?) photodynamic therapy potentially offers much higher treatment selectivity than its one-photon (1-?) counterpart. By utilizing focused light for 2-? excitation, treatment volumes on the order of microliters can be achieved thus maximizing localized insult to abnormal blood vessels and sparing healthy tissue. We propose that 2-? photodynamic therapy will be valuable in the treatment of choroidal neovascularization secondary to age related macular degeneration as well as other conditions. To ascertain feasibility of 2-? photodynamic therapy we measured 2-? spectrum and cross sections of verteporfin (80 GM at 940 nm, 1 GM = 10 -50 cm 4s/photon), chlorin e6 (14 GM at 800 nm) and tetrasulfonated aluminum phthalocyanine (140 GM at 900 nm) and investigated their in vitro efficiency under 2-? excitation. Only verteporfin demonstrated cell kill under the used irradiation parameters (average light intensity 9.1 mW, wavelength 850 nm, total light dose 6900 J/cm2). Dorsal skinfold window chamber model in mouse was used to test efficiency of 2-? PDT with verteporfin in vivo. Although we were able to induce photodynamic damage to a blood vessel using 1-? excitation, 2-? excitation resulted in no visible damage to irradiated blood vessel. The most probable reason is low efficiency of verteporfin as a 2-? photosensitizer. We also report 2-? spectrum of new photosensitizer, HCC4 (4300 GM at 830 nm), specifically designed for efficient 2-? excitation.

  10. Apoptosis triggered by pyropheophorbide-? methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

    NASA Astrophysics Data System (ADS)

    Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

    2014-06-01

    A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-? methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

  11. Efficiency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense.

    PubMed

    Baldea, Ioana; Olteanu, Diana Elena; Bolfa, Pompei; Ion, Rodica Mariana; Decea, Nicoleta; Cenariu, Mihai; Banciu, Manuela; Sesarman, Alina Viorica; Filip, Adriana Gabriela

    2015-10-01

    Photodynamic therapy (PDT) could be an adjuvant therapy in melanoma, an aggressive cancer that arises from melanocytes. Several reports showed encouraging results of the efficacy of PDT in melanoma on experimental models and in clinical trials. Therefore, we studied the efficacy of two derivatives of tetraphenylporphyrin (TPP): meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THOPP) and meso-5-(4-hydroxyphenyl)-10,15,20-tris (4-methoxyphenyl) porphyrin (THOMPP) as photosensitizers for PDT, compared to FDA approved delta aminolevulinic acid (ALA) against a lightly pigmented, melanoma cell line, WM35, in vitro. Both porphyrins were more efficient as photosensitizers, compared to ALA, without dark toxicity. The efficiency depended on the intracellular localization and the molecule structure. THOPP, the most efficient porphyrin localized mainly in mitochondria, while THOMPP accumulated in lysosomes; both showed melanosomal localization. The symmetric THOPP molecule was able to generate increased oxidative stress damage and apoptosis. THOPP also induced a low effect on the defense mechanisms like antioxidant enzyme SOD (superoxide dismutase), NF-kB (nuclear transcription factor kB) activation and MITF (microphthalmia transcription factor). The lower efficiency of the asymmetric molecule, THOMPP was probably due to a diminished photoactivation, which led to a lower ROS induced damage, combined with higher activation of the defense mechanisms. PMID:26257158

  12. [Hyperbaric therapy and diving medicine - hyperbaric therapy part 2: adjuvant therapy].

    PubMed

    Tetzlaff, Kay; Jüttner, Björn

    2015-10-01

    Hyperbaric oxygen therapy (HBOT), i.?e. breathing pure oxygen at elevated ambient pressure, remains the gold standard of care in treating air or gas embolism and decompression illness. Guidelines are less clear on the value of HBOT in acute management of carbon monoxide (CO) poisoning or clostridial necrosis. To evaluate the evidence of clinical efficacy of HBOT we performed a systematic literature review. Part 1 assesses acute indications such as air or gas embolism, decompression sickness, CO-poisoning, clostridialmyonecrosis, necrotizing problem wounds, acute traumatic wounds and arterial retinal occlusion. Part 2 discusses further uses of HBOT as adjuvant treatment and highlights problems in assessing the value of HBOT using evidence-based medicine criteria. PMID:26510108

  13. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy

    PubMed Central

    Cheng, Yuhao; Cheng, Hao; Jiang, Chenxiao; Qiu, Xuefeng; Wang, Kaikai; Huan, Wei; Yuan, Ahu; Wu, Jinhui; Hu, Yiqiao

    2015-01-01

    Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer 1O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of 1O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design. PMID:26525216

  14. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy.

    PubMed

    Cheng, Yuhao; Cheng, Hao; Jiang, Chenxiao; Qiu, Xuefeng; Wang, Kaikai; Huan, Wei; Yuan, Ahu; Wu, Jinhui; Hu, Yiqiao

    2015-01-01

    Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen ((1)O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer (1)O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of (1)O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design. PMID:26525216

  15. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

    NASA Astrophysics Data System (ADS)

    Nelius, Thomas; de Riese, Werner T. W.

    2003-06-01

    Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

  16. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  17. Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea

    NASA Astrophysics Data System (ADS)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

    2003-10-01

    Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

  18. Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections

    PubMed Central

    Baltazar, Ludmila M.; Ray, Anjana; Santos, Daniel A.; Cisalpino, Patrícia S.; Friedman, Adam J.; Nosanchuk, Joshua D.

    2015-01-01

    Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes. PMID:25821448

  19. [Intraoperative fluorescent detection and photodynamic therapy in patients with metastatic cerebral lesions].

    PubMed

    Kurzhupov, M I; Loshakov, V A; Filonenko, E V; Za?tsev, A M; Khanmurzaeva, A G

    2012-01-01

    Brain metastases are known to have poor prognosis. In spite of using modern treatments such as microsurgical resection, radiotherapy, chemotherapy, survival of these patients remains low. Due to this fact we looked for novel methods of treatment that are able to increase the recurrence-free surgical and therefore overall survival of these patients. This paper analyzes new treatment methods used in brain tumors--fluorescent detection and photodynamic therapy with 5-aminolevulinic acid. PMID:22708435

  20. Effective near-infrared photodynamic therapy assisted by upconversion nanoparticles conjugated with photosensitizers

    PubMed Central

    Dou, Qing Qing; Teng, Choon Peng; Ye, Enyi; Loh, Xian Jun

    2015-01-01

    A drug model photosensitizer–conjugated upconversion nanoparticles nanocomplex was explored for application in near-infrared photodynamic therapy. As near-infrared penetrates deeper into the tissue, the model is useful for the application of photodynamic therapy in deeper tissue. The nanocomplex that was synthesized had low polydispersity, and the upconversion nanoparticle was covalently conjugated with the photosensitizer. The robust bond could prevent the undesired premature release of photosensitizer and also enhance the singlet-oxygen generation. Singlet-oxygen generation rate from this nanocomplex was evaluated in solution. The photodynamic therapy effect was assessed with MCF-7 cells in two different methods, 3-(4,5-dimethylth-iazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead assay. The assay results showed that promising efficacy (>90%) can be achieved with a low concentration (50 ?g mL?1) of this nanocomplex and mild dosage (7 mW cm?2) of near-infrared laser treatment. PMID:25609954

  1. Androgen Receptor Targeted Conjugate for Bimodal Photodynamic Therapy of Prostate Cancer in Vitro.

    PubMed

    Rapozzi, Valentina; Ragno, Daniele; Guerrini, Andrea; Ferroni, Claudia; della Pietra, Emilia; Cesselli, Daniela; Castoria, Gabriella; Di Donato, Marzia; Saracino, Emanuela; Benfenati, Valentina; Varchi, Greta

    2015-08-19

    Prostate cancer (PC) represents the most common type of cancer among males and is the second leading cause of cancer death in men in Western society. Current options for PC therapy remain unsatisfactory, since they often produce uncomfortable long-term side effects, such as impotence (70%) and incontinence (5-20%) even in the first stages of the disease. Light-triggered therapies, such as photodynamic therapy, have the potential to provide important advances in the treatment of localized and partially metastasized prostate cancer. We have designed a novel molecular conjugate (DR2) constituted of a photosensitizer (pheophorbide a, Pba), connected to a nonsteroidal anti-androgen molecule through a small pegylated linker. This study aims at investigating whether DR2 represents a valuable approach for PC treatment based on light-induced production of single oxygen and nitric oxide (NO) in vitro. Besides being able to efficiently bind the androgen receptor (AR), the 2-trifluoromethylnitrobenzene ring on the DR2 backbone is able to release cytotoxic NO under the exclusive control of light, thus augmenting the general photodynamic effect. Although DR2 is similarly internalized in cells expressing different levels of androgen receptor, the AR ligand prevents its efflux through the ABCG2-pump. In vitro phototoxicity experiments demonstrated the ability of DR2 to kill cancer cells more efficiently than Pba, while no dark toxicity was observed. Overall, the presented approach is very promising for further development of AR-photosensitizer conjugates in the multimodal photodynamic treatment of prostate cancer. PMID:26108715

  2. Nanoparticulate carriers for photodynamic therapy of cholangiocarcinoma: In vitro comparison of various polymer-based nanoparticles.

    PubMed

    Grünebaum, Jonas; Söbbing, Judith; Mulac, Dennis; Langer, Klaus

    2015-12-30

    The photodynamic therapy with porphyrin derivatives is an established approach to targeted tumor therapy, but is still afflicted with disadvantages of the physicochemical characteristics of the photosensitizer. To overcome drug-related restrictions in photodynamic therapy, three 5,10,15,20-tetrakis(m-hydroxyphenyl) porphyrin (mTHPP)-loaded nanoparticulate formulations based on poly(dl-lactide-co-glycolide) (PLGA), poly(d,l-lactide) (PLA), and Eudragit(®) E were prepared in a consistent diameter range and compared with free mTHPP in vitro. Formulation behavior was investigated in two different cholangiocellular cell lines, EGI-1 and TFK-1. High cytotoxicity was shown for all photosensitizer loaded nanoparticle (NP) formulations and free mTHPP, with EC50 values ranging from 0.2 to 1.3?M. PLA based NP were not as effective in all performed tests as other formulations. Nanoparticulate embedded mTHPP remained photodynamically active and resulted in caspase-3 activation even at low concentrations of 250nM. PLGA based NP exhibited highest caspase-3 activation. For all formulations an effective intracellular accumulation of mTHPP was observed, whereby for mTHPP-Eudragit(®) E-NP a 200-fold drug accumulation was shown. Polymer based nanoparticles were shown to be an effective and highly active transport vehicle for the photosensitizer mTHPP in vitro. Problems like low solubility of free drug can be circumvented by successful embedding into nanoparticulate carrier systems, maintaining therapeutic effects of the photosensitizer. PMID:26456264

  3. 131I-Zn-Chlorophyll derivative photosensitizer for tumor imaging and photodynamic therapy.

    PubMed

    Ocakoglu, Kasim; Er, Ozge; Kiyak, Guven; Lambrecht, Fatma Yurt; Gunduz, Cumhur; Kayabasi, Cagla

    2015-09-30

    In recent years, the photodynamic therapy studies have gained considerable attention as an alternative method to surgery, chemotherapy and radiotherapy which is commonly used to fight cancer. In this study, biological potentials of a benzyloxy bearing zinc(II) pheophorbide-a (Zn-PH-A) were investigated via in vivo and in vitro experiments. Zn-PH-A was labeled with (131)I with high efficiency (95.3 ± 2.7%) and its biodistribution studies were investigated on female Albino Wistar rats. The radiolabeled photosensitizer had been intravenously injected into the tail vein, and then the animals were sacrificed at 30, 60 and 120 min post injection. The percent of radioactivity per gram of organs (%ID/g) was determined. The radiolabeled Zn-PH-A showed high uptake in ovary. In addition, photodynamic therapy studies of the photosensitizer were conducted in EMT6, murine mammary carcinoma and HeLa, human cervix carcinoma cell lines. For the photodynamic therapy studies, the cells with Zn-PH-A were exposed to red light (650 nm) at the doses of 10-30 J/cm(2). The results showed that Zn-PH-A has stronger PDT effect in EMT6 than HeLa cell. Our present work demonstrates (131)I-labeled photosensitizer as a bifunctional agent (PDT and nuclear imaging) which could be improved in future by using EMT6 growing tumor in nude mice. PMID:26226337

  4. Effectiveness of antimicrobial photodynamic therapy on staphylococcus aureus using phenothiazinium dye with red laser

    NASA Astrophysics Data System (ADS)

    Monteiro, Juliana S. C.; de Oliveira, Susana C. P. S.; Pires-Santos, Gustavo M.; Sampaio, Fernando José P.; Zanin, Fátima Antônia A.; Pinheiro, Antônio L. B.

    2015-03-01

    The aim of this study was to evaluate in vitro the bactericidal effect of Antimicrobial Photodynamic Therapy - AmPDT using a phenothiazinium compound (toluidine blue O and methylene blue, 12.5 ?g/mL) on Staphylococcus aureus (ATCC 23529) irradiated or not with the red laser (? 660 nm, 12J/cm2). All tests were performed in triplicate and samples distributed into the following groups: Negative control, Laser, Photosensitizer, and AmPDT. Bactericidal effect of the Antimicrobial Photodynamic Therapy was assessed by counting of colony-forming units and analyzed statistically (ANOVA, Tukey test, p<0.05). The results showed, comparing the Laser group with Negative control, a statistically significant increase of counting on the Laser group (p = 0.003). The use of the photosensitizer alone reduced the mean number of CFU (64.8%) and its association with the Laser light resulted in 84.2% of inhibition. The results are indicative that the use of Antimicrobial Photodynamic Therapy presented in vitro bactericidal effect on Staphylococcus aureus.

  5. Accelerated migration and invasion of prostate cancer cells after a photodynamic therapy-like challenge: Role of nitric oxide.

    PubMed

    Fahey, Jonathan M; Girotti, Albert W

    2015-09-15

    Employing an in vitro model for 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), we recently reported that human prostate cancer PC3 cells rapidly and persistently overexpressed inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate ALA/light challenge. The upregulated iNOS/NO was shown to play a key role in cell resistance to apoptotic photokilling and also in the dramatic growth spurt observed in surviving cells. In the present study, we found that PC3 cells surviving an ALA/light insult not only proliferated faster than non-stressed controls, but migrated and invaded faster as well, these effects being abrogated by an iNOS inhibitor or NO scavenger. Photostressed prostate DU145 cells exhibited similar behavior. Using in-gel zymography, we showed that PC3 extracellular matrix metalloproteinase-9 (MMP-9) was strongly activated 24 h after ALA/light treatment and that MMP-9 inhibitor TIMP-1 was downregulated, consistent with MMP-9 involvement in enhanced invasiveness. We also observed a photostress-induced upregulation of ?6 and ?1 integrins, implying their involvement as well. The MMP-9, TIMP-1, and integrin effects were strongly attenuated by iNOS inhibition, confirming NO's role in photostress-enhanced migration/invasion. This study reveals novel, potentially tumor-promoting, side-effects of prostate cancer PDT which may be averted through use of iNOS inhibitors as PDT adjuvants. PMID:26068242

  6. [Adjuvant systemic antibiotic therapy for surgically treated spondylodiscitis].

    PubMed

    Marmelstein, D; Homagk, N; Hofmann, G O; Röhl, K; Homagk, L

    2015-04-01

    Recognised methods for the treatment of spondylodiscitis in correspondence to the immobilisation are systemic antibiotic therapy. However, the available data for recommendations of specific antibiotic therapy are very heterogeneous. The aim of this study was to focus on the adjuvant antibiotic therapy in surgical treated cases of spondylodiscitis and to reach a guideline regarding its application in patients' spondylodiscitis. Between 01.10.1998 and 31.12.2011 276 inpatient cases of spondylodiscitis were surgically treated, documented and included in the study. The study involved medical history, germ status, localisation and extent of spondylodiscitis and antibiotic treatment. Between 01.01.2012 and 31.12.2013 a further 20 cases of spondylodiscitis were treated according to a standardised treatment regimen of antibiotic therapy and included in the study. The age distribution shows a marked prominence of 60 to 80 year-olds, with a leading localisation of spondylodiscitis in the lumbar spine with 55?% followed by the thoracic spine (33?%) and the cervical spine (12?%). A constant observation during the study periods was the delayed diagnosis of more than 1 month of spondylodiscitis, so that about 60?% of the patients were not receiving any treatment for their disease at the time of hospitalisation. The aetiology of spondylodiscitis is very heterogeneous and remained unknown in 34?% of cases. However, diabetes mellitus appeared as a disease favouring the occurrence of spondylodiscitis since it was concomitant with almost 50?% of patients with spondylodiscitis. The bacterial spectrum is limited in our area to staphylococci, with a predominance of Staphylococcus aureus. At least about 10?% of the germs are multi-drug resistant. In 45?% of cases, pathogen detection was unsuccessful. Clindamycin is the most commonly used antibiotic in the treatment of spondylodiscitis and is used in 26.8?% in combinations with other antibiotics. The antibiotic therapy is administered for at least for 3 months. The significant decrease in inflammatory markers in the course of treatment shows the positive response of patients to therapy. The recommendations for antibiotic treatment of spondylodiscitis are very heterogeneous, so our goal is to standardise the therapy without reducing the quality and effectiveness of treatment. The results show that the calculated antibiotic therapy (CAT) with clindamycin is reasonable in the treatment of spondylodiscitis especially with the predominance of Staphylococcus aureus as pathogen. In addition, suitable antibiotic therapy should be administered in correspondence to a culture and sensitivity testing and should be maintained for at least 12 weeks, even when a reduction of inflammatory markers by 50?% after 2 weeks has already been achieved. It is noteworthy to point out the high probability of coexistence of spondylodiscitis with diabetes mellitus, so that spondylodiscitis should always be considered in diabetic patients with back pain and increased levels of inflammatory markers. A significant reduction in the very long time until reaching a definitive diagnosis should be achieved. PMID:25874395

  7. Hypoxia Induced by Upconversion-Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors.

    PubMed

    Liu, Yanyan; Liu, Yong; Bu, Wenbo; Cheng, Chao; Zuo, Changjing; Xiao, Qingfeng; Sun, Yong; Ni, Dalong; Zhang, Chen; Liu, Jianan; Shi, Jianlin

    2015-07-01

    Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia. PMID:26012928

  8. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Z. X.; Huang, Y. Z.; Shi, S. G.; Tang, S. H.; Li, D. H.; Chen, X. L.

    2014-07-01

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

  9. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  10. [Effect of preoperative adjuvant therapy of esophageal carcinoma].

    PubMed

    Shiozaki, H; Ogawa, Y; Ogawa, M; Fujimoto, J; Kido, Y; Miyamoto, T; Tane, H; Kokunai, I; Ueno, K; Kobayashi, K

    1984-10-01

    Between January 1970 and December 1983, 148 patients of esophageal carcinoma were treated surgically in the 2nd Department of Surgery, Osaka University Medical School. Among these patients, 70 (48.6%) with suspected invasion to neighboring structures were treated with preoperative chemotherapy, radiotherapy or a combination of both. The chemotherapeutic agents used were tegafur (FT-207)-suppository, bleomycin (BLM) or peplomycin (PEP). Radiotherapy (3000-4000 cGy) for selected cases was begun at the same time as the chemotherapy. Three to four weeks after the chemotherapy and radiotherapy were completed, esophagectomy was performed. The effects of the preoperative adjuvant therapies were investigated in these patients, and the following results were obtained: A marked histological effect, according to the Guide Lines in Clinical and Pathologic Studies for Carcinoma of the Esophagus (Japanese Society for Esophageal Diseases, 1976) was found in 47.4% of the radiotherapy plus FT-207 group, 39.1% of the group receiving radiotherapy alone and 28.6% of the group receiving radiotherapy plus PEP or BLM. Radiotherapy plus FT-207 showed excellent effects (77.8% of this group showed marked histological effects) on well differentiated squamous cell carcinoma, as shown histologically by biopsy specimens. Tumors exhibiting sharp edged margins radiographically and endoscopically, showed a very good histological effect after preoperative radiotherapy. Metastatic lymph nodes present in the irradiation field, whose primary lesion showed a marked histological effect, also gave excellent results. Postoperative radiotherapy is also expected to be equally effective on these cases. PMID:6207778

  11. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  12. Adjuvant therapy use among Appalachian breast cancer survivors.

    PubMed

    Tan, Xi; Marshall, Vincent D; Anderson, Roger T; Donohoe, Joseph; Camacho, Fabian; Balkrishnan, Rajesh

    2015-07-01

    There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival.A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline-recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) ?0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model.About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio = 2.82, P < 0.001) and a lower risk of nonpersistence (hazard ratio = 0.40, P < 0.001). Drug-related side effects like pain may be an important factor leading to nonadherence and early discontinuation. In addition, aromatase inhibitor (AI) adherence and persistence were significantly influenced by out-of-pocket drug costs, dual eligibility status, and coverage gaps. Nonadherence to and nonpersistence with AET were associated with higher risks of all-cause mortality.Our findings of suboptimal AET adherence/persistence in Appalachia as well as positive associations between AET adherence/persistence and overall survival outcomes further underscore the importance of ensuring appropriate AET use in this population to reduce breast cancer mortality disparities. Our findings also suggest that intervention strategies focusing on individualized treatment and medication-related factors may improve adjuvant treatment use. PMID:26131828

  13. Adjuvant therapy use among Appalachian breast cancer survivors

    PubMed Central

    Tan, Xi; Marshall, Vincent D.; Anderson, Roger T.; Donohoe, Joseph; Camacho, Fabian; Balkrishnan, Rajesh

    2015-01-01

    Abstract There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival. A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline-recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) ?0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model. About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio?=?2.82, P?adjuvant treatment use. PMID:26131828

  14. In Vivo Near-Infrared Photodynamic Therapy Based on Targeted Upconversion Nanoparticles.

    PubMed

    Zhou, Aiguo; Wei, Yanchun; Chen, Qun; Xing, Da

    2015-11-01

    Upconversion nanoparticles have shown to be a promising prospect for biological detection and photodynamic therapy (PDT). The focus of this study was to develop an upconversion nanoparticle modified with a targeting peptide and photosensitizer for near-infrared photodynamic therapy. To produce a tumor-targeting nanophotosensitizer with near-infrared excitation, NaYF4:Yb/Er upconversion nanoparticles were first wrapped with O-carboxymethyl chitosan to develop an upconversion rianoplatform and then chemically conjugated with the photosensitizer pyropheophorbide-a (Ppa) and RGD peptide c(RGDyK). The nanoparticle exhibited low dark toxicity and high biocompatibility. When injected into the tail vein of tumor-bearing U87-MG mice, UCNP-Ppa-RGD revealed an enhanced tumor-specific biodistribution and successful therapeutic effect following near-infrared laser irradiation. It possessed a significantly deeper therapeutic depth compared with conventional visible light triggered PDT using Ppa. The results suggest that the nanoplatform has advantages in the spectral application, and the constructed tumor-specific nanoparticle shows high clinical potential to serve not only as a photodynamic imaging reagent but also as a therapeutic agent for the treatment of large or deeply seated tumors. PMID:26554158

  15. Endonyx toenail onychomycosis caused by Trichophyton rubrum: treatment with photodynamic therapy based on methylene blue dye*

    PubMed Central

    Souza, Linton Wallis Figueiredo; Souza, Simone Vilas Trancoso; Botelho, Ana Cristina de Carvalho

    2013-01-01

    This study shows the effectiveness of photodynamic therapy based on methylene blue dye for the treatment of endonyx toenail onychomycosis. Four patients with endonyx onychomycosis caused by Trichophyton rubrum were treated with 2% methylene blue aqueous solution irradiated with light emission diode at 630 nm and an energy density of 36 J/cm2 for 6 months at 2-week intervals. The preliminary study showed the effectiveness of this therapy in the treatment of endonyx onychomycosis, and also indicated that the disease can be caused by T. rubrum. PMID:24474123

  16. Is Photodynamic Therapy an Effective Treatment for Periodontal and Peri-Implant Infections?

    PubMed

    Sculean, Anton; Aoki, Akira; Romanos, George; Schwarz, Frank; Miron, Richard J; Cosgarea, Raluca

    2015-10-01

    Antimicrobial photodynamic therapy (PDT) has attracted much attention for the treatment of pathogenic biofilm associated with peridontitis and peri-implantitis. However, data from randomized controlled clinical studies (RCTs) are limited and, to some extent, controversial, making it difficult to provide appropriate recommendations. Therefore, the aims of the present study were (a) to provide an overview on the current evidence from RCTs evaluating the potential clinical benefit for the additional use of PDT to subgingival mechanical debridement (ie, scaling and root planing) alone in nonsurgical periodontal therapy; and (b) to provide clinical recommendations for the use of PDT in periodontal practice. PMID:26427570

  17. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    NASA Astrophysics Data System (ADS)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  18. Early experience in MRI-guided therapies of prostate cancer: HIFU, laser and photodynamic treatment

    PubMed Central

    Da Rosa, M.R.; Trachtenberg, J.; Chopra, R.

    2011-01-01

    Abstract Prostate cancer screening has resulted in earlier diagnosis with lower-grade disease, leading to over-detection and over-treatment in a significant number of patients. Current whole-gland radical treatments are associated with significant rates of morbidity. The high prevalence of low-risk disease together with an inability to accurately identify those men harboring more aggressive cancers has led to tremendous research in low-morbidity focal therapies for prostate cancer. This review summarizes the early experiences with focal therapy with emphasis on early applications of laser, high-intensity focuses ultrasound, and photodynamic approaches. PMID:22187023

  19. Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Liu, Kai; Yang, Guangbao; Cheng, Liang; He, Lu; Liu, Yumeng; Li, Yonggang; Guo, Liang; Liu, Zhuang

    2014-07-01

    Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02495h

  20. Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy

    PubMed Central

    Mfouo-Tynga, Ivan; Abrahamse, Heidi

    2015-01-01

    The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events. PMID:25955645

  1. Vaginal Speculum For Photodynamic Therapy And Method Of Using The Same

    DOEpatents

    Tadir, Yona (Irvine, CA); Berns, Michael W. (Trabuco Canyon, CA); Monk, Brad J. (Long Beach, CA); Profeta, Glen (Rancho Santa Margarita, CA); Tromberg, Bruce J. (Irvine, CA)

    1995-10-17

    An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.

  2. The Role of Subcellular Localization in Initiation of Apoptosis by Photodynamic Therapy

    PubMed Central

    Kessel, David; Luo, Yu; Deng, Yongqi; Chang, C. K.

    2015-01-01

    Rapid initiation of apoptosis can be induced by photodynamic therapy, depending on the cell line and sensitizer employed. In this study, we evaluated the photodynamic responses to two structurally related photosensitizing agents, using the P388 murine leukemia cell line in culture. Photodamage mediated by tin etiopurpurin involved lysosomes and mitochondria and yielded a rapid apoptotic response; apoptotic nuclei were observed within 60 min after PDT. A drug analog, tin octaethylpurpurin amidine, targeted lysosomes, mitochondria and cell membranes; apoptotic nuclei were not observed until 24 h after PDT. These results, together with other recent reports, are consistent with the hypothesis that membrane photodamage can delay or prevent an apoptotic response to PDT. PMID:9077123

  3. Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department*

    PubMed Central

    Cabete, Joana; Rafael, Margarida; Cravo, Mariana; Moura, Cecília; Sachse, Fernanda; Pecegueiro, Manuela

    2015-01-01

    BACKGROUND Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

  4. Photodynamic therapy by nonresonant two-photon excitation

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Riemann, Iris; Fischer, Peter

    1999-07-01

    Intracellular photodynamic reactions by nonlinear excitation of porphyrin photosensitizers have been induced using near infrared ultrashort laser pulses at 200 fs pulse width, 80 MHz pulse repetition rate and 2 mW mean laser power. In particular, a highly focused 780 nm pulsed laser scanning beam was employed at a frame rate of 1/16 s-1 (60 microsecond(s) pixel dwell time) to expose Photofrin-labeled and aminolevulinic acid (ALA)-labeled Chinese hamster ovary cells. Intracellular accumulation and photobleaching of the fluorescent photosensitizers protoporphyrin IX and Photofrin have been studied by non-resonant two-photon fluorescence excitation. Subsequent scanning of the sensitizer-labeled cells resulted in reduced cloning efficiency of 50% and 0% after about 13 scans (approximately equals 10 mJ) and 50 scans, respectively, in the case of Photofrin accumulation (5 (mu) g/ml) and after about 24 scans and 100 scans in the case of ALA administration (1.5 mg/ml). Live/dead assays revealed the loss of vitality of most of cells after 50 scans for Photofrin-labeled cells and 100 scans for ALA-labeled cells. Sensitizer-free control cells could be scanned more than 250 times (1.1 h) without impact on the reproduction behavior, morphology, and vitality.

  5. In vitro cellular effects of ?-aminolevulinic acid sensitized photodynamic therapy

    NASA Astrophysics Data System (ADS)

    He, Xiao-Yan; Jacques, Steven L.; Thomsen, Sharon L.

    1994-07-01

    In this study, the subcellular targets and cellular mechanisms of the photodynamic action of (delta) -aminolevulinic acid (5ALA) were investigated in rat mammary carcinoma cells (MTF7) in vitro. A constant dose of 5ALA (200 (mu) g/ml) was given and the light dose was varied (20-480 J/cm2). The effects of PDT were examined at 0 hr, 3 hr, and 24 hr after the treatment using the following assays: (1) Trypan Blue Dye Exclusion Assay for cell membrane damage; (2) MTT Assay for mitochondrial damage; (3) 3H-Thymidine Incorporation Assay for DNA synthesis; (4) Cell Colony Formation Assay for cell survival. The MTT and colony formation assays are the best predictors of cell survival early and late after treatment. Cell membrane damage and almost complete disruption of mitochondrial function are early mechanisms of 5ALA PDT cytopathic effect. Reduction of DNA synthesis is a later, and possibly, a secondary effect of disruption of mitochondrial function although this conjecture has to be explored further. Reduction of DNA synthesis and cell membrane damage show complicated relationships with light dose while loss of mitochondrial function and long term survival are essentially complete with the lowest light dose used in this study.

  6. Clinical and experimental results of photodynamic therapy in neurosurgery

    NASA Astrophysics Data System (ADS)

    Kostron, Herwig; Hochleitner, B. W.; Obwegeser, Alois; Seiwald, M.

    1995-03-01

    Since 1984, 58 patients bearing malignant brain tumors were treated 70 times with photodynamic treatment (PDT). The patient population consisted of 11 primary glioblastoma WHO grade IV, 39 recurrent glioblastomas, 3 malignant meningiomas, 3 recurrent melanomas, and 2 metastasis of carcinomas. The patients were sensitized with hematoporphyrin derivative (HPD) 2.5 mg/bodyweight 24 - 48 hours prior to craniotomy and tumor resection. The light-irradiation was performed by an Argon pumped dye laser (Aurora M) superficially and/or interstitially at a dose ranging up to 250 J/cm2. The median survival of primary glioblastomas was 19 months and for recurrent glioblastomas 7 months, respectively. Malignant meningiomas, as well as melanomas, did not benefit from PDT, whereas one patient with a metastasis of an adenocarcinoma is still recurrence free since 18 months, the other recurred after 6 months. HPD extractions of the tumor revealed significantly different concentrations among the various tumors, but also between identical histologies. The survival, however, did not correlate with the HPD concentration in the tumor. PDT prolongs median survival of primary glioblastomas significantly, and doubles the survival of recurrent high grade gliomas. Furthermore the treatment of recurrent low grade gliomas and metastasis to the brain are promising indications for PDT.

  7. Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model

    NASA Astrophysics Data System (ADS)

    Menyaev, Yulian A.; Zharov, Vladimir P.

    2006-02-01

    One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 ?m wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.

  8. An irradiation system for photodynamic therapy with a fiber-optic sensor for measuring tissue oxygen

    NASA Astrophysics Data System (ADS)

    Quintanar, L.; Fabila, D.; Stolik, S.; de la Rosa, J. M.

    2013-11-01

    Photodynamic Therapy is a well known treatment based on the interaction of light of specific wavelength with a photosensitizing drug. In the presence of oxygen molecules, the illumination of the photosensitizer can activate the production of reactive oxygen species, which leads to the death of target cells within the treated tissue. In order to obtain the best therapy response, the tissue oxygen concentration should be measured to adjust the therapy parameters before and during the treatment. In this work, an irradiation system for 5-Aminolevulinic Acid Photodynamic Therapy is presented. It allows the application of visible light radiation of 630 nm using as a light source a high-brightness light emitting diode with an optical-power automatic control considering a light depth-distribution model. A module to measure the tissue oxygen saturation has been implemented into the system. It is based on two light emitting diodes of 660 nm and 940 nm as light sources, a photodiode as a detector and a new handheld fiber optic reflectance pulse oximetry sensor for estimating the blood oxygen saturation within the tissue. The pulse oximetry sensor was modeled through multilayered Monte Carlo simulations to study the behavior of the sensor with changes in skin thickness and melanin content.

  9. Solitary giant neurofibroma of the neck subjected to photodynamic therapy: case study

    PubMed Central

    2012-01-01

    Photodynamic therapy (PDT) - the fourth modality - has been successfully used in the management of early and advanced pathologies of the head and neck. We studied the effect of this modality on a giant solitary neurofibroma of the neck. A 70-year-old Caucasian female presented with left neck pain and disfigurement associated with slight shortness of breath and dysphagia. Examination revealed a large mass in the neck with no neurovascular compromise. Magnetic resonance imaging (MRI) reported a heterogeneously enhancing mass extending from the left angle of the mandible to the base of the neck. A core biopsy was performed and histopathological examination revealed a disorganised array of peripheral nerve fascicles. The patient elected to receive photodynamic therapy as the primary intervention. The multi-disciplinary meeting approved the treatment plan. The photosensitizing agent was mTHPC (0.15?mg/kg), which was systemically administered 96-hours prior to ultrasound (US)-guided light delivery to the mass, which was undertaken under general anaesthesia. Recovery was uneventful.Post-PDT follow-up showed that the patient’s pain, dysphagia and shortness of breath issues had improved. The disfigurement of the neck caused by the mass was no longer a problem. Three months post-PDT, MRI revealed a significant reduction in the neurofibroma size. PDT was proven as a successful primary intervention for this pathology. However, higher evidence-based studies are required before this therapy can be proposed as a replacement to any of the other conventional therapies. PMID:22673101

  10. Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform

    PubMed Central

    Dai, Tianhong; Fuchs, Beth B.; Coleman, Jeffrey J.; Prates, Renato A.; Astrakas, Christos; St. Denis, Tyler G.; Ribeiro, Martha S.; Mylonakis, Eleftherios; Hamblin, Michael R.; Tegos, George P.

    2012-01-01

    Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. PMID:22514547

  11. Efficacy of photodynamic therapy against larvae of Aedes aegypti: confocal microscopy and fluorescence-lifetime imaging

    NASA Astrophysics Data System (ADS)

    de Souza, L. M.; Pratavieira, S.; Inada, N. M.; Kurachi, C.; Corbi, J.; Guimarães, F. E. G.; Bagnato, V. S.

    2014-03-01

    Recently a few demonstration on the use of Photodynamic Reaction as possibility to eliminate larvae that transmit diseases for men has been successfully demonstrated. This promising tool cannot be vastly used due to many problems, including the lake of investigation concerning the mechanisms of larvae killing as well as security concerning the use of photosensitizers in open environment. In this study, we investigate some of the mechanisms in which porphyrin (Photogem) is incorporated on the Aedes aegypti larvae previously to illumination and killing. Larvae at second instar were exposed to the photosensitizer and after 30 minutes imaged by a confocal fluorescence microscope. It was observed the presence of photosensitizer in the gut and at the digestive tract of the larva. Fluorescence-Lifetime Imaging showed greater photosensitizer concentration in the intestinal wall of the samples, which produces a strong decrease of the Photogem fluorescence lifetime. For Photodynamic Therapy exposition to different light doses and concentrations of porphyrin were employed. Three different light sources (LED, Fluorescent lamp, Sun light) also were tested. Sun light and fluorescent lamp shows close to 100% of mortality after 24 hrs. of illumination. These results indicate the potential use of photodynamic effect against the LARVAE of Aedes aegypti.

  12. Conscious sedation with inhaled 50% nitrous oxide/oxygen premix in photodynamic therapy sessions for vulvar lichen sclerosus treatment*

    PubMed Central

    Cabete, Joana; Campos, Sara; Lestre, Sara

    2015-01-01

    Photodynamic therapy has been described as an effective therapeutic option in selected cases of anogenital lichen sclerosus that are refractory to first-line treatments. However, procedure-related pain is a limiting factor in patient adherence to treatment. The authors report the case of a 75-year-old woman with highly symptomatic vulvar lichen sclerosus, successfully treated with photodynamic therapy. An inhaled 50% nitrous oxide/oxygen premix was administered during sessions, producing a pain-relieving, anxiolytic, and sedative effect without loss of consciousness. This ready-to-use gas mixture may be a well-tolerated and accepted alternative to classical anesthetics in Photodynamic therapy, facilitating patients' adherence to illumination of pain-prone areas. PMID:25672311

  13. SU-E-T-191: First Principle Calculation of Quantum Yield in Photodynamic Therapy

    SciTech Connect

    Abolfath, R; Guo, F; Chen, Z; Nath, R

    2014-06-01

    Purpose: We present a first-principle method to calculate the spin transfer efficiency in oxygen induced by any photon fields especially in MeV energy range. The optical pumping is mediated through photosensitizers, e.g., porphyrin and/or ensemble of quantum dots. Methods: Under normal conditions, oxygen molecules are in the relatively non-reactive triplet state. In the presence of certain photosensitizer compounds such as porphyrins, electromagnetic radiation of specific wavelengths can excite oxygen to highly reactive singlet state. With selective uptake of photosensitizers by certain malignant cells, photon irradiation of phosensitized tumors can lead to selective killing of cancer cells. This is the basis of photodynamic therapy (PDT). Despite several attempts, PDT has not been clinically successful except in limited superficial cancers. Many parameters such as photon energy, conjugation with quantum dots etc. can be potentially combined with PDT in order to extend the role of PDT in cancer management. The key quantity for this optimization is the spin transfer efficiency in oxygen by any photon field. The first principle calculation model presented here, is an attempt to fill this need. We employ stochastic density matrix description of the quantum jumps and the rate equation methods in quantum optics based on Markov/Poisson processes and calculate time evolution of the population of the optically pumped singlet oxygen. Results: The results demonstrate the feasibility of our model in showing the dependence of the optical yield in generating spin-singlet oxygen on the experimental conditions. The adjustable variables can be tuned to maximize the population of the singlet oxygen hence the efficacy of the photodynamic therapy. Conclusion: The present model can be employed to fit and analyze the experimental data and possibly to assist researchers in optimizing the experimental conditions in photodynamic therapy.

  14. Alteration of photosensitizer content and parameters of free radical reactions in a patient's blood under photodynamic therapy of malignant tumors

    NASA Astrophysics Data System (ADS)

    Lubchenko, G. N.; Chichuk, Tatyana V.; Stranadko, Eugeny P.

    1999-12-01

    The purpose of this study was to determine the changes in concentrations of the two Russian photosensitizers in blood plasma of patients under Photodynamic therapy. In this work were used two sensitizers of domestic production: Photohem (hematoporphyrin derivative) and Photosense (sulfonated aluminium phtalocyanine). It was found that one month after injection the concentrations of the photosensitizers in blood plasma remained high enough. Was shown alteration of level of apo-(beta) -lipoproteins oxidation and antioxidant activity of blood plasma under the influence of Photodynamic therapy.

  15. Progress in the development of photodynamic-therapy-generated cancer vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai

    2003-07-01

    Upon giving an outline on vaccines in general, their history and priorities for future development, this paper gives a brief summary of the advances in the generation of cancer vaccines from the first attempts made over 100 years ago to those currently evaluted in clinical trials. This is followed by discussing hte intitial achievements in the investigation of cancer vaccines generated by photodynamic therapy (PDT). Recent contributions from our research to the understanding of how PDT-generated cancer vaccines work and their advantages compared to other types of cancer vaccines are discussed.

  16. Near Infrared Light-Triggered Drug Generation and Release from Gold Nanoparticle Carriers for Photodynamic Therapy

    PubMed Central

    Cheng, Yu; Doane, Tennyson L.; Chuang, Chi-Hung; Ziady, Assem; Burda, Clemens

    2014-01-01

    A photoprecursor Pc 227 is covalently bound onto gold nanoparticles (Au NPs) to produce the known photodynamic therapy (PDT) drug Pc 4 upon 660 nm photoirradiation. The photochemical formation of the photoproduct Pc 4 is identified by spectroscopy, chromatography, and mass spectrometry and its PDT efficacy is equal to Pc 4 when administered non-covalently by Au NPs, with the added benefit of improved covalent delivery and targeted NIR-triggered release from the covalent Pc 227-Au NP conjugate, while during transport the attached Pc 227 is quenched by the Au NP and PDT inactivated. PMID:24515950

  17. 808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Xue, Bin; Kong, Xianggui; Tu, Langping; Liu, Xiaomin; Zhang, Youlin; Chang, Yulei; Luo, Yongshi; Zhao, Huiying; Zhang, Hong

    2014-11-01

    The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd3+ doped UCNPs with 808 nm excitation properties rely on a thick Nd3+ sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved.The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd3+ doped UCNPs with 808 nm excitation properties rely on a thick Nd3+ sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved. Electronic supplementary information (ESI) available: TEM images, XRD patterns and NIR emission spectra of UCNPs. See DOI: 10.1039/c4nr04953e

  18. Simultaneous measurement of photosensitizer absorption and fluorescence in patients undergoing photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Stratonnikov, Alexander A.; Ermishova, Natalia V.; Meerovich, Gennadii A.; Kudashev, Boris V.; Vakoulovskaya, Elena G.; Loschenov, Victor B.

    2002-05-01

    This paper deals with photosensitizer quantification in patients undergoing photodynamic therapy. Both fluorescence and diffuse reflectance spectroscopy were applied to evaluate concentration of sulphonated aluminum phthalocyanine in different tissues. The mixtures of Intralipid, blood and photosensitizer with different concentrations were used as standard samples to solve the problem in question. While fluorescence method is more sensitive and more convenient to apply in clinics, the absorption technique may be applied to non fluorescent dyes and used to evaluate the shifts in adsorption peak position due to interaction of dye with tissues. Finally, the concentration dynamics of non fluorescent dye (cobalt phthalocyanine) in patients was obtained with the use of absorption method alone.

  19. The role of porphyrin chemistry in tumor imaging and photodynamic therapy.

    PubMed

    Ethirajan, Manivannan; Chen, Yihui; Joshi, Penny; Pandey, Ravindra K

    2011-01-01

    In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references). PMID:20694259

  20. Photodynamic therapy on bladder cancer cells: further studies on the performance of Coimbra sensitizers

    NASA Astrophysics Data System (ADS)

    d'A. Rocha Gonsalves, Antonio M.; Serra, Arménio C.; Pineiro, Marta; Botelho, M. Filomena

    2010-04-01

    Following previous studies where we developed some high performance porphyrin derivatives for photodynamic therapy demonstrating their activity in different cell lines, we now extend our attention to CRL1472 bladder cancer line. In this work the phototoxicity of several diaryl and tetraarylporphyrins with different structures were evaluated with different incubation times. The phototoxicity observed was not directly related to the concentration of photosensitizer inside cells. Uptake studies demonstrate that the brominated derivative 2 which despite the most efficient photosensitizer presents a poor tendency to enter into cells.

  1. Role of the scanning laser ophthalmoscope in photodynamic therapy of macular disease

    NASA Astrophysics Data System (ADS)

    Van de Velde, Frans J.

    2000-06-01

    Photodynamic therapy (PDT) is a new treatment modality for exudative forms of age-related maculopathy. It can be combined with others types of selective or conventional laser therapy. Imaging and functional testing with the scanning laser ophthalmoscope (SLO) are important for detailed diagnostic information as well as for the interpretation of the long term outcome of different treatment strategies. For example, infrared imaging in a confocal mode superbly outlines areas of minimal edema due to slow leakage and switching of wavelengths enables simultaneous and repeated angiographic studies of the retina with the same instrument. Visual acuities are strongly influenced by background illuminance and binocular fixation patterns, and absolute but not incremental microperimetric thresholds measure correctly the functional status of the photoreceptor-pigment epithelium complex. The scanning laser ophthalmoscope has been adapted for use as a delivery system in microphotocoagulation and photodynamic therapy. A non- scanning external therapeutic laser source uses the same Maxwellian view entrance location into the eye as the SLO. Advantages include a non-contact delivery, fixation control, registration of treatment locations, and the possibility to spatially modulate the area being treated.

  2. The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances

    SciTech Connect

    Zawacka-Pankau, Joanna Krachulec, Justyna Grulkowski, Ireneusz Bielawski, Krzysztof P. Selivanova, Galina

    2008-11-01

    Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently extensively investigated as a promising strategy for highly specific anti-cancer therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely used compounds due to their potent biophysical and biochemical properties. Recent data suggest that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p53-dependent cell death both in the dark and upon irradiation. In this review we describe the available evidence on the role of p53 in PDT.

  3. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-08-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  4. Combining magnetic hyperthermia and photodynamic therapy for tumor ablation with photoresponsive magnetic liposomes.

    PubMed

    Di Corato, Riccardo; Béalle, Gaëlle; Kolosnjaj-Tabi, Jelena; Espinosa, Ana; Clément, Olivier; Silva, Amanda K A; Ménager, Christine; Wilhelm, Claire

    2015-03-24

    The ongoing nanotech revolution has the potential to transform diagnostic and therapeutic methods. Stimuli-triggered nanotherapies based on remotely activated agents have become attractive alternatives to conventional chemotherapy. Herein, we designed an optimized smart nanoplatform based on dually loaded hybrid liposomes to achieve enhanced tumor therapy. The aqueous core was highly loaded with iron oxide nanoparticles, while the lipid bilayer was supplied with a photosensitizer payload. The double cargo translated into double functionality: generation of singlet oxygen under laser excitation and heat production under alternating magnetic field stimulation, coupling photodynamic therapy (PDT) to magnetic hyperthermia (MHT). These liposomes address both therapeutic agents within tumor cells, and the combined PDT/MHT therapy resulted in complete cancer cell death in vitro while total solid-tumor ablation was achieved in an in vivo rodent model. PMID:25695371

  5. Optimization of Adjuvant Radiation in Breast Conservation Therapy: Can We Minimize without Compromise?

    PubMed Central

    Edwards-Bennett, Sophia M.; Correa, Candace R.; Harris, Eleanor E.

    2011-01-01

    Adjuvant breast radiation therapy after breast conservation surgery is recommended as it yields significant reduction in the risk of local recurrence, and confers a potential overall survival benefit. Although the standard breast radiation regimen has historically been delivered over 5–7 weeks; more novel, shorter courses of breast radiation are currently being employed, offering the advantage of more convenience and less time-commitment. Herein, we review the recent literature substantiating these abbreviated radiation treatment approaches and the methods of delivery thereof. In addition, we discuss imaged guided techniques currently being utilized to further refine the delivery of adjuvant breast radiation therapy. PMID:22295217

  6. Virus Capsids as Targeted Nanoscale Delivery Vessels of Photoactive Compounds for Site-Specific Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Cohen, Brian A.

    The research presented in this work details the use of a viral capsid as an addressable delivery vessel of photoactive compounds for use in photodynamic therapy. Photodynamic therapy is a treatment that involves the interaction of light with a photosensitizing molecule to create singlet oxygen, a reactive oxygen species. Overproduction of singlet oxygen in cells can cause oxidative damage leading to cytotoxicity and eventually cell death. Challenges with the current generation of FDA-approved photosensitizers for photodynamic therapy primarily stem from their lack of tissue specificity. This work describes the packaging of photoactive cationic porphyrins inside the MS2 bacteriophage capsid, followed by external modification of the capsid with cancer cell-targeting G-quadruplex DNA aptamers to generate a tumor-specific photosensitizing agent. First, a cationic porphyrin is loaded into the capsids via nucleotide-driven packaging, a process that involves charge interaction between the porphyrin and the RNA inside the capsid. Results show that over 250 porphyrin molecules associate with the RNA within each MS2 capsid. Removal of RNA from the capsid severely inhibits the packaging of the cationic porphyrins. Porphyrin-virus constructs were then shown to photogenerate singlet oxygen, and cytotoxicity in non-targeted photodynamic treatment experiments. Next, each porphyrin-loaded capsid is externally modified with approximately 60 targeting DNA aptamers by employing a heterobifunctional crosslinking agent. The targeting aptamer is known to bind the protein nucleolin, a ubiquitous protein that is overexpressed on the cell surface by many cancer cell types. MCF-7 human breast carcinoma cells and MCF-10A human mammary epithelial cells were selected as an in vitro model for breast cancer and normal tissue, respectively. Fluorescently tagged virus-aptamer constructs are shown to selectively target MCF-7 cells versus MCF-10A cells. Finally, results are shown in which porphyrin-virus-aptamer constructs selectively target and kill cancer cells versus non-cancer cells. Specifically, the results show that MS2 is a viable candidate as an addressable nanodelivery vessel of photoactive compounds, and the implications are that the nucleotide-driven packaging approach for modifying MS2 can be used to impart new functionalities for a host of diagnostic or therapeutic applications.

  7. NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

    2014-09-01

    The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

  8. Determination of the optical properties of vascular tissues: potential applications in vascular-targeting photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Tian, Yongbin; Chen, Ping; Lin, Lie; Huang, Zheng; Tang, Guoqing; Xu, Heping

    2007-11-01

    It has been proven that photodynamic therapy (PDT) is effective in treating various malignant and non-malignant diseases. In the treatment of certain non-malignant vascular diseases, such as wet age-related macular degeneration (AMD) and port wine stains (PWS), unlike in the treatment of malignant solid tumors, light irradiation usually starts immediately after the intravenous (IV) injection of photosensitizers while the photosensitizers is mainly circulating inside blood vessels. Under such vascular-targeting action mode, photoreactions between photosensitizers and light can selectively destruct the vascular tissues. Light distribution is complex so that it is important to understand the optical properties of targeted vessels and surrounding tissues. To better determine the optical properties of vascular tissues, we developed a tissue-simulating phantom and adopted frequency-domain measurement of phase difference. Absorption and reduced scattering coefficients in blood vessels were estimated and light distribution was simulated by the Monte Carlo method. These determinations are essential for the implication of better light dosimetry models in clinical photodynamic therapy and vascular-targeting PDT, in particular.

  9. Photodynamic Therapy for Cancer and for Infections: What Is the Difference?

    PubMed Central

    Sharma, Sulbha K.; Mroz, Pawel; Dai, Tianhong; Huang, Ying-Ying; St. Denis, Tyler G.; Hamblin, Michael R.

    2012-01-01

    Photodynamic therapy (PDT) was discovered over one hundred years ago when it was observed that certain dyes could kill microorganisms when exposed to light in the presence of oxygen. Since those early days, PDT has mainly been developed as a cancer therapy and as a way to destroy proliferating blood vessels. However, recently it has become apparent that PDT may also be used as an effective antimicrobial modality and a potential treatment for localized infections. This review discusses the similarities and differences between the application of PDT for the treatment of microbial infections and for cancer lesions. Type I and type II photodynamic processes are described, and the structure-function relationships of optimal anticancer and antimicrobial photosensitizers are outlined. The different targeting strategies, intracellular photosensitizer localization, and pharmacokinetic properties of photosensitizers required for these two different PDT applications are compared and contrasted. Finally, the ability of PDT to stimulate an adaptive or innate immune response against pathogens and tumors is also covered. PMID:23248387

  10. Simultaneous photodynamic and photothermal therapy using photosensitizer-functionalized Pd nanosheets by single continuous wave laser.

    PubMed

    Zhao, Zengxia; Shi, Saige; Huang, Yizhuan; Tang, Shaoheng; Chen, Xiaolan

    2014-06-11

    In this work, we prepared chlorin e6 (Ce6)-functionalized Pd nanosheets (Pd-PEI-Ce6) for the photodynamic and photothermal combined therapy that use a single laser. To fabricate the Pd-PEI-Ce6 nanocomposite, photosensitizer Ce6 were chemically conjugated to polyethylenimine (PEI) and the formed Ce6-PEI conjugates were then anchored onto Pd nanosheets by electrostatic and coordination interaction. The prepared Pd-PEI-Ce6 nanocomposite were about 4.5 nm in size, exhibited broad, and strong absorption from 450 to 800 nm, good singlet oxygen generation capacity and photothermal conversion efficiency, and excellent biocompability. Significantly greater cell killing was observed when HeLa cells incubated with Pd-PEI-Ce6 were irradiated with the 660 nm laser, attributable to both Pd nanosheets-mediated photothermal ablation and the photodynamic destruction effect of photosensitizer Ce6. The double phototherapy effect was also confirmed in vivo. It was found that the Pd-PEI-Ce6 treated tumor-bearing mice displayed the enhanced therapeutic efficiency compared to that of Pd-PEI, or Ce6-treated mice. Our work highlights the promise of using Pd nanosheets for potential multimode cancer therapies. PMID:24801639

  11. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  12. 808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging.

    PubMed

    Wang, Dan; Xue, Bin; Kong, Xianggui; Tu, Langping; Liu, Xiaomin; Zhang, Youlin; Chang, Yulei; Luo, Yongshi; Zhao, Huiying; Zhang, Hong

    2015-01-01

    The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd(3+) doped UCNPs with 808 nm excitation properties rely on a thick Nd(3+) sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved. PMID:25406514

  13. Study of the efficacy of 5-ALA mediated photodynamic therapy on human rhabdomyosarcoma cell line (RD)

    NASA Astrophysics Data System (ADS)

    Atif, M.; Fakhar-e-Alam, M.; Firdous, S.; Zaidi, S. S. Z.; Suleman, R.; Ikram, M.

    2010-10-01

    The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the Rhabdomyosarcoma (RD) cell line. The present study evaluates the effects of photodynamic therapy (PDT) with 5-ALA as photosensitizer using human muscle cancer cells as experimental model. We study the photosensitizer uptake, cytotoxicity, phototoxicity, and cellular viability of the RD cells which was estimated by means of neutral-red spectrophotometric assay. The given experiment was consisted of two steps. For the first one, RD cells were exposed to 5-ALA at concentrations of 0 up to 1000 ?g of ALA/ml in minimum essential medium (MEM). The optimal uptake of photosensitizer (5-ALA) in RD cells was investigated by means of spectrometric measurements. Cells viability was determined by means of neutral red assay (NRA). In the second step, 5-ALA exposed RD cells were irradiated with red light (a diode laser, ? = 635 nm) at total light dose of 80 J/cm2. The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the viability of RD cells were investigated. It was observed that sensitizer concentration or light doses have no significant effect on cells viability when studied independently. The maximal cellular uptake occurred after 47 hours in vitro incubation. The phototoxic assay showed that ALA-PDT induced killing of 76% of the cells at 250 ?g/ml drug dose and 80 J/cm2 light dose.

  14. Integral photodynamic therapy of bladder cancer using 5-ALA and white light

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold; Waidelich, Raphaela; Beyer, Wolfgang; Stepp, Herbert G.; Knuechel-Clarke, Ruth; Hofstetter, Alfons

    2005-04-01

    We report on clinical experiences with photodynamic therapy in patients with recurrent, multifocal superficial transitional cell carcinoma of the urinary bladder. PDT is performed by intravesically applied 5-aminolevulinic acid and a Xe arc lamp as a light source delivering more than 5 Watt white light for activation of 5-ALA induced Protoporphyrin IX. For whole bladder wall irradiation a special irrigation catheter system has been developed. Based on that technology we determined whether this treatment modality was effective in destroying urothelial carcinoma and preventing recurrent disease. The study should help defining the optimal target group of patients and is considered as basis for a long term and multicenter clinical trial. The initial clinical results indicate that white light photodynamic therapy with 5-ALA is an effective organ-preserving procedure for treating multifocal superficial transitional cell carcinoma of the bladder, even in patients with refractory urothelial carcinoma and is effective in selectively destroying flat neoplastic lesions like carcinoma in situ. None of the patients showed phototoxic skin reactions or loss of bladder capacity.

  15. Sulfonated aluminum phthalocyanines for two-photon photodynamic cancer therapy: the effect of the excitation wavelength

    NASA Astrophysics Data System (ADS)

    Wang, J.; Li, W.; Yu, H. B.; Cheung, N. H.; Chen, J. Y.

    2014-03-01

    Sulfonated aluminum phthalocyanine (AlPcS) is a well-studied photosensitizer which has been widely used in research and in clinical applications of the photodynamic therapy of cancers. Conventionally, one-photon excitation was used, but it was unknown whether two-photon excitation of AlPcS was equally effective. In this study, the two-photon absorption cross sections of AlPcS at near infrared wavelengths were deduced from femtosecond (fs) laser-induced fluorescence. We found that the two-photon absorption cross section of AlPcS was strongly dependent on the excitation wavelength. It was about 19 GM when excited at 800 nm, but grew to 855 GM when excited at 750 nm. The 750 nm fs-laser-induced fluorescence images of AlPcS in human nasopharyngeal carcinoma cells were clearly visible while the corresponding images were very dim when excited at 800 nm. Singlet oxygen production was 13 times higher when excited at 750 nm relative to 800 nm. Our subsequent in vitro experiments showed that 750 nm two-photon excitation with an unfocused fs laser beam damaged cancer cells in a light-dose-dependent manner typical of photodynamic therapy (PDT). The killing at 750 nm was about 9-10 times more efficient than at 800 nm. These results demonstrated for the first time that AlPcS has good potential for two-photon PDT of cancers.

  16. Enhancement of protoporphyrin IX performance in aqueous solutions for photodynamic therapy.

    PubMed

    Homayoni, Homa; Jiang, Ke; Zou, Xiaoju; Hossu, Marius; Rashidi, Leila Hossein; Chen, Wei

    2015-06-01

    Molecular modification of protoporphyrin IX (PpIX) was conducted to improve its water solubility and therapeutic performance for photodynamic therapy. The carboxylic acid and the two nitrogen atoms in the core of PpIX molecule were protonated following by conjugation with 3-aminopropyl triethoxysilane (APTES). Then, folic acid (FA) was conjugated to the APTES-coated PpIX (MPpIX) through chemical bonding between FA and protonated PpIX. The results showed that APTES coating can stabilize PpIX and increase its water solubility. Consequently, this leads to the enhancement in luminescence and singlet oxygen production. Upon X-ray irradiation, singlet oxygen can be detected in the MPpIX but not in PpIX. This means that MPpIX can be used for deep cancer treatment as X-ray can penetrate deeply into tissue. Molecular modification also reduces the dark toxicity of PPIX and increases their cell uptake. All these traits indicate that the Molecular modification of PpIX may potentially improve the efficacy of photodynamic therapy for cancer treatment. PMID:25636780

  17. Zinc(II) phthalocyanine loaded PLGA nanoparticles for photodynamic therapy use.

    PubMed

    Ricci-Júnior, Eduardo; Marchetti, Juliana Maldonado

    2006-03-01

    Sophisticated delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (Np) were prepared using a solvent emulsion evaporation method (SEEM) to load zinc(II) phthalocyanine (ZnPc). Np were obtained using poly (D,L latic-co-glycolic acid) (PLGA). ZnPc is a second generation of photoactive agents used in photodynamic therapy. ZnPc loaded PLGA nanoparticles were prepared by SEEM, characterized and available in cellular culture. The process yield and encapsulation efficiency were 80 and 70%, respectively. The nanoparticles have a mean diameter of 285 nm, a narrow size distribution with polydispersive index of 0.12, smooth surface and spherical shape. ZnPc loaded nanoparticles maintains its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained with a moderate and burst effect of 15% for 3 days. The photocytotoxicity of ZnPc loaded PLGA Np was evaluated on P388-D1 cells what were incubated with ZnPc loaded Np (5 microM) by 6h and exposed to red light (675 nm) for 120 s, and light dose of 30 J/cm(2). After 24h of incubation, the cellular viability was determined, obtaining 61% of cellular death. All the physical-chemical, photophysical and photobiological measurements performed allow us conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for photodynamic therapy. PMID:16442755

  18. Results of photodynamic therapy in the combined treatment of choroidal metastasis

    NASA Astrophysics Data System (ADS)

    Likhvantseva, Vera G.; Osipova, Ekaterina V.; Petrenko, Mikhail V.; Merzlyakova, Oksana Y.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    Choroidal metastasis (CM) are more and more spreading type of eye's neoplasma. The frequency of CM is increasing with prolonging of cancer patients' life. And it makes worse the quality of their life because blindness. Photodynamic therapy (PDT) is very delicate modality, which can be used for this purpose. The aim of this work was to open the possibility and to determine the efficacy of photodynamic therapy (PDT) in the treatment of patients with CM. PDT was performed simultaneously with standard chemotherapy in 8 oncological patients with CM. We used photosensitizer Photosens in doses of 0.3 mg/kg and light doses 150 J/cm2 (675 nm). PDT was performed in the some stances. Its are ranged from 7 to 10. Complete tumor regression was achieved in 6 cases. The high retina ablation was developed in one case. And in one case effect was not complete: tumor size reduced from 5 mm to 3 mm of thickness. We didn't notice any recurrence for 6-18 months follow-up. PDT is modality that could to be used in the in the combined treatment of the CM.

  19. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    NASA Astrophysics Data System (ADS)

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  20. Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy.

    PubMed

    Bhana, Saheel; Lin, Gan; Wang, Lijia; Starring, Hunter; Mishra, Sanjay R; Liu, Gang; Huang, Xiaohua

    2015-06-01

    We present the synthesis and application of a new type of dual magnetic and plasmonic nanostructures for magnetic-field-guided drug delivery and combined photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold nanopopcorns containing a self-assembled iron oxide cluster core were prepared via a seed-mediated growth method. The hybrid nanostructures are superparamagnetic and show great photothermal conversion efficiency (?=61%) under near-infrared irradiation. Compact and stable nanocomplexes for photothermal-photodynamic therapy were formed by coating the nanoparticles with near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. The nanocomplex showed enhanced release and cellular uptake of the photosensitizer with the use of a gradient magnetic field. In vitro studies using two different cell lines showed that the dual mode photothermal and photodynamic therapy with the assistance of magnetic-field-guided drug delivery dramatically improved the therapeutic efficacy of cancer cells as compared to the combination treatment without using a magnetic field and the two treatments alone. The "three-in-one" nanocomplex has the potential to carry therapeutic agents deep into a tumor through magnetic manipulation and to completely eradicate tumors by subsequent photothermal and photodynamic therapies without systemic toxicity. PMID:25965727

  1. Modulation of ROS production in photodynamic therapy using a pH controlled photoinduced electron transfer (PET) based sensitiser.

    PubMed

    Atchison, Jordan; Kamila, Sukanta; McEwan, Conor; Nesbitt, Heather; Davis, James; Fowley, Colin; Callan, Bridgeen; McHale, Anthony P; Callan, John F

    2015-12-01

    A new sensitiser () for use in photodynamic therapy (PDT) has been developed to enable control of ROS production as a function of pH. This pH dependent PDT behaviour was tested in HeLa cells and in SCID mice bearing human xenograft pancreatic cancer (BxPC-3) tumours. PMID:26435142

  2. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; ?iplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  3. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation.

    PubMed

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-01-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce (1)O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of (1)O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility. PMID:25105845

  4. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation

    PubMed Central

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-01-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility. PMID:25105845

  5. Evaluation of photodynamic therapy using a diode laser and different photosensitizers against enterococcus faecalis.

    PubMed

    Silva, Emmanuel J; Coutinho-Filho, Wagner P; Andrade, Aurimar O; Herrera, Daniel R; Coutinho-Filho, Tauby S; Krebs, Renato L

    2014-01-01

    Photodynamic therapy (PDT) has been proven to be effective in disinfecting root canals. The aim of this present study was to evaluate the effects of PDT on the viability of Enterococcus faecalis using methylene blue (MB) and malachite green (MG) as photosensitizers. Solutions containing E. faecalis (ATCC 29212) were prepared and harvested by centrifugation to obtain cell suspensions, which were mixed with MB and MG. Samples were individually irradiated by the diode laser at a distance of 1mm for 30, 60, or 120 seconds. Colonyforming units (CFU) were determined for each treatment. PDT for 60 and 120 seconds with MG reduced E. faecalis viability significantly. Similar results were obtained when MB was used as photosensitizer. PDT using MB and MG have antibacterial effect against E. faecalis, showing potential to be used as an adjunctive antimicrobial procedure in endodontic therapy. PMID:25523956

  6. Optimization of irradiance for photodynamic therapy of port-wine stain

    NASA Astrophysics Data System (ADS)

    Zhang, Feng-juan; Hu, Xiao-ming; Zhou, Ya; Li, Qin

    2015-04-01

    Controllable and effective irradiation of lesions is among the key factors that affect the potency of photodynamic therapy (PDT). An optimization method for the irradiance distribution of treatment was proposed which can be used to improve the efficacy of PDT and allow more lesions to receive the desired irradiance level in a single therapy session. With the proposed digital illumination binocular treatment system, the preferred surface normal vectors, irradiation angles, as well as area and weight coefficients of lesions can be achieved and used as characteristic parameters to optimize the irradiation direction. Two port-wine stain phantom experiments were performed. The comparison of the illumination area between preoptimization and postoptimization showed that the proposed method can effectively guide the light source control, improve the distribution of light dose, and increase the effective treatment area.

  7. Regression of drusen after combined treatment using photodynamic therapy with verteporfin and ranibizumab.

    PubMed

    Novais, Eduardo Amorim; Badaró, Emmerson; Regatieri, Caio Vinicius Saito; Duker, Jay; de Oliveira Bonomo, Pedro Paulo

    2015-02-01

    Drusen are the clinical hallmark of age-related macular degeneration. The regression of these deposits in patients treated with argon, krypton, or diode laser photocoagulation has been reported previously. However, previous protocols with conventional laser for drusen may result in retinal pigment epithelium (RPE) damage and unwanted scotomas. The authors report a case of complete regression of soft drusen in a 65-year-old man with central visual loss and metamorphopsia due to a drusenoid RPE detachment and soft drusen who underwent reduced-fluence photodynamic therapy (PDT) and three monthly intravitreal injections of ranibizumab. Reduced-fluence PDT combined with anti-VEGF therapy may reduce drusen without inducing RPE cell damage. PMID:25707058

  8. Lanthanide-doped upconversion nanoparticles electrostatically coupled with photosensitizers for near-infrared-triggered photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Chen, Zhuo; Zheng, Wei; Zhu, Haomiao; Lu, Shan; Ma, En; Tu, Datao; Zhou, Shanyong; Huang, Mingdong; Chen, Xueyuan

    2014-06-01

    Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a ?-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy.Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a ?-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy. Electronic supplementary information (ESI) available: Tables S1 and S2 and Fig. S1-S13. See DOI: 10.1039/c4nr01826e

  9. Mechanisms in photodynamic therapy: part two—cellular signaling, cell metabolism and modes of cell death

    PubMed Central

    Castano, Ana P.; Demidova, Tatiana N.; Hamblin, Michael R.

    2013-01-01

    Summary Photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In the second of a series of three reviews, we will discuss the mechanisms that operate in PDT on a cellular level. In Part I [Castano AP, Demidova TN, Hamblin MR. Mechanism in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 2004;1:279–93] it was shown that one of the most important factors governing the outcome of PDT, is how the photosensitizer (PS) interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. PS can localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes. An explosion of investigation and explorations in the field of cell biology have elucidated many of the pathways that mammalian cells undergo when PS are delivered in tissue culture and subsequently illuminated. There is an acute stress response leading to changes in calcium and lipid metabolism and production of cytokines and stress proteins. Enzymes particularly, protein kinases, are activated and transcription factors are expressed. Many of the cellular responses are centered on mitochondria. These effects frequently lead to induction of apoptosis either by the mitochondrial pathway involving caspases and release of cytochrome c, or by pathways involving ceramide or death receptors. However, under certain circumstances cells subjected to PDT die by necrosis. Although there have been many reports of DNA damage caused by PDT, this is not thought to be an important cell-death pathway. This mechanistic research is expected to lead to optimization of PDT as a tumor treatment, and to rational selection of combination therapies that include PDT as a component. PMID:25048553

  10. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    SciTech Connect

    Showalter, Timothy N.; Ohri, Nitin; Teti, Kristopher G.; Foley, Kathleen A.; Keith, Scott W.; Trabulsi, Edouard J.; Lallas, Costas D.; Dicker, Adam P.; Hoffman-Censits, Jean; Pizzi, Laura T.; Gomella, Leonard G.

    2012-02-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  11. Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

    SciTech Connect

    Krishnan, Sunil Rana, Vishal; Evans, Douglas B.; Varadhachary, Gauri; Das, Prajnan; Bhatia, Sumita; Delclos, Marc E.; Janjan, Nora A.; Wolff, Robert A.; Crane, Christopher H.; Pisters, Peter W.

    2008-03-01

    Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

  12. Anti-tumor immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT.

  13. Laser surgery and medicine including photodynamic therapy in China today

    NASA Astrophysics Data System (ADS)

    Li, Junheng

    2000-10-01

    The development of laser medicine in China is correlated with the development of laser science in China. After the first Chinese laser, ruby laser came into being in 1961, Chinese medical scientists began to do the studies about laser medicine in the middle 1960s. For example, ruby laser was adopted for the retina coagulation experiment in 1965. Since 1970s, through the free choice of utilizing Co2, He-Ne, Nd:YAG argon, ruby lasers, laser surgery and medicine has been widely applied to the treatment for diseases of the eyes, ENT, dermatology, surgery, gynecology, tumors and diseases suitable to physical therapy or acupuncture with satisfactory effects. In June 1977, a nation-wide laser medicine symposium was held at Wuhan, Hubei Province with 200 participants including medical doctors and laser technologies from 23 provinces and municipal towns. Till the end of seventies, utilization of lasers has been extended to Nd glass laser, N laser and tunable dye lasers. The scope covered most of the clinical sections. After Dr. Thomas J. Dougherty developed the PDT for cancers in Roswell Park Memorial Institute in Buffalo in late 1970s and Professor Yoshihiro Hayata successfully applied the PDT in clinical treatment for lung cancer in 1980, Chinese pharmacists successfully produced the Chinese HpD and the first case of PDT, a lower eyelid basal cell carcinoma patient was treated with the Chinese laser equipment in 1981 in Beijing. Its success brought attention establishing a research group supported by the government in 1982. The members of the group consisted the experts on preclinical and clinical research, pharmaceutical chemistry, laser physicists and technologists. A systemic research on PDT was then carried out and obvious result was achieved. The step taken for PDT also accelerated the researchers on other kinds of laser medicine and surgery because the medical doctors had begun to master the knowledge about laser science. The prosperous situation of rapid development of laser science, bio-medical lasers, laser medicine and surgery as well as PDT was prolonged in the whole nineteen eighties.

  14. The effect of photodynamic therapy on the mechanical integrity of normal rabbit carotid arteries.

    PubMed

    Grant, W E; Buonaccorsi, G; Speight, P M; MacRobert, A J; Hopper, C; Bown, S G

    1995-08-01

    Photodynamic therapy (PDT) for tumor ablation is effective in the treatment of superficial cancers. Adjunctive intraoperative PDT has been proposed for the "sterilization" of tumor beds after the resection of malignancies. Arteries in photosensitized animal models exposed to appropriate light receive characteristic injury. This study was conducted to determine whether photodynamic injury to the rabbit carotid artery results in thrombotic occlusion or weakening of the vessel wall. PDT of the carotid arteries of New Zealand white rabbits, using either disulphonated aluminum phthalocyanine or 5-aminolevulinic-acid-induced protoporphyrin IX as the photosensitizer, was performed with a light dose of 100 J/cm2. Histologic examination of the carotids treated with either agent demonstrated typical full-thickness loss of cellularity 3 days after PDT. All vessels remained patent, and no inflammatory infiltrate was evident. Elastin van Gieson staining showed preservation of inner and medial elastic laminae and medial and adventitial collagen. Additional rabbits were similarly treated with PDT to 1-cm segments of both common carotid arteries. The animals were sacrificed at 3, 7, and 21 days. The carotids were exposed, and both control and treated segments were subjected to intraluminal hydrostatic distention until the vessels burst. No reduction in the pressure required to burst the vessels was evident in the treated vessels as compared with the control vessels. The authors of the study concluded that despite full-thickness cell death, PDT-treated arteries are not at risk for thrombotic occlusion or hemorrhage. PMID:7630302

  15. Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

    NASA Astrophysics Data System (ADS)

    Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

    2012-02-01

    Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 ?L/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

  16. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

    PubMed

    Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

    2015-01-01

    Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS. PMID:26604753

  17. The photodynamic therapy effect of aluminum and zinc tetrasulfophthalocyanines on melanoma cancer cells

    NASA Astrophysics Data System (ADS)

    Maduray, K.; Karsten, A.; Odhav, B.; Nyokong, T.

    2010-11-01

    Photodynamic therapy (PDT) represents a novel treatment that uses a photosensitizer (PS), light source (laser) of an appropriate wavelength and oxygen to induce cell death in cancer cells. The aim of this study was to investigate the photodynamic effects of aluminum tetrasulfophthalocyanines (AlTSPc) and zinc (ZnTSPc) tetrasulfophthalocyanines activated with a 672nm wavelength laser on melanoma cancer, dermal fibroblast and epidermal keratinocyte cells. Each cell line was photosensitized with either AlTSPc or ZnTSPc for 2 h before using a diode laser with a wavelength of 672nm to deliver a light dose of 4.5 J/cm2 to the cells. The cell viability of melanoma cells were decreased to approximately 50% with concentrations of 40 ?g/ml for AlTSPc and 50 ?g/ml for ZnTSPc. These PS concentrations caused a slight decrease in the cell viability of fibroblast and keratinocyte cells. Both photosensitizers in the presence of high concentrations (60 ?g/ml-100 ?g/ml) showed cytotoxicity effects on melanoma cells in its inactive state. This was not observed in fibroblast and keratinocyte cells. Cell death in PDT treated melanoma cells was induced by apoptosis. Therefore, AlTSPc and ZnTSPc exhibit the potential to be used as a PS in PDT for the treatment of melanoma cancer.

  18. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

    PubMed Central

    Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

    2015-01-01

    Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS. PMID:26604753

  19. Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy.

    PubMed Central

    Ceckler, T. L.; Gibson, S. L.; Kennedy, S. D.; Hill, R.; Bryant, R. G.

    1991-01-01

    Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (Pi) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in Pi were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in Pi resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned a near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis. Images Figure 4 PMID:1829953

  20. The potential application of photodynamic therapy in drug-resistant tuberculosis.

    PubMed

    Chang, Ji-Eun; Oak, Chul-Ho; Sung, Nackmoon; Jheon, Sanghoon

    2015-09-01

    Tuberculosis (TB) is an infectious bacterial disease that has historically created a high global health burden. Unfortunately, the emergence of drug-resistant TB (DR-TB), which includes multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), has greatly affected the treatment of TB. Anti-TB chemotherapy drugs are classified into five groups to facilitate application of effective guidelines for the treatment regimen. However, chemotherapy has a limited ability to treat DR-TB, and therefore a novel alternative treatment for DR-TB is required. In this review, we focused on photodynamic therapy (PDT) as potential treatment for DR-TB. PDT is a widely used cancer treatment that combines photosensitizers and harmless laser light to produce reactive oxygen species that selectively damage the target cells. Initially, PDT was originally developed to target pathogenic microorganisms but fell into disuse because of adverse reactions. Recently, photodynamic antimicrobial chemotherapy is attracting attention again as an alternative treatment for bacterial infections. In our previous study, we suggested that PDT could be a novel option to treat MDR- and XDR-TB in vitro. Despite the limited previous studies regarding PDT in TB models, fast-developing bronchoscopic technologies and clinician experience will soon facilitate the clinical application of safe and minimally invasive PDT for TB. PMID:25907636

  1. Pheophorbide a mediated photodynamic therapy against human epidermoid carcinoma cells (A431)

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Chun; Li, Wen-Tyng

    2011-02-01

    The objective of this study was to characterize the death mechanism of human epidermoid carcinoma cells (A431) triggered by photodynamic therapy (PDT) with pheophorbide a. First of all, significant inhibition on the survival of A431 cells (< 20 %) was observed when an irradiation dose of 5.1 J/cm2 combined with 125 ng/ml of pheophorbide a was applied. Survival rate of human keratinocyte cells was over 70 % under the same PDT parameters, suggesting that pheophorbide a killed cancer cells selectively. Mitochondria were the main target sites where pheophorbide a accumulated. Formation of reactive oxygen species (ROS) was detected after PDT. Addition of antioxidant N-Acetyl cysteine prevented ROS production and increased cell survival thereafter. The decrease in cellular ATP level was also observed at 6 hrs after PDT. Typical apoptotic cellular morphology and a collapse of mitochondrial membrane potential occurred after PDT. The loss of mitochondrial membrane potential led to the release of cytochrome c from the mitochondria to the cytosol, followed by activation of caspase-9 and caspase-3. The activation of caspase-3 resulted in poly(ADP-ribose) polymerase (PARP) cleavage in A431 cells, followed by DNA fragmentation. In conclusion, the results demonstrated that pheophorbide a possessed photodynamic action against A431 cells, mainly through apoptosis mediated by mitochondrial intrinsic pathway triggered by ROS.

  2. Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer

    PubMed Central

    Acedo, P; Stockert, J C; Cañete, M; Villanueva, A

    2014-01-01

    Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6?J/cm2, respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24?h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone). PMID:24625981

  3. Fiber optic probes for tissue illumination in photodynamic diagnosis and therapy

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold; Beyer, Wolfgang; Friedsam, G.; Jocham, Dieter; Noack, Axel; Sroka, Ronald; Stepp, Herbert G.; Unsoeld, Eberhard

    1992-08-01

    Photodynamic diagnosis (PDD) and therapy (PDT) require light application devices which enable homogeneous illumination of tissue in hollow organs. Three techniques based on modification of the aperture of single fibers are presented mainly for use in urology and pneumology in combination with rigid and flexible endoscopes. All illumination systems allow for nearly entire illumination of the endoscope's viewing field. A microlens system is used for fluorescence diagnostic purposes in the lung. The system, consisting of two plano convex lenses in a condenser configuration, is attached directly to the fiber. The beam profile is optimized by ray tracing calculations. For fluorescence excitation of the tumormarker Photofrin II in the urinary bladder a 500 micrometers plastic fiber is used. The tip of the fiber is polished to a double cone with angles of 12 degree(s) and 7 degree(s). With this modification the aperture is increased by a factor of two. Photodynamic treatment of confined superficial tumors in the lung was successfully performed with a fused silica fiber coupled to the endoscope in a special adaptive device. In this procedure laserlight at 630 nm is guided through the optics channel of rigid endoscopes. A homogeneous circular illumination pattern is obtained following exactly the deflection angle of the endoscope.

  4. Photodynamic therapy of endometriosis with HpD (Photosan III) in a new in vitro model

    NASA Astrophysics Data System (ADS)

    Viereck, Volker; Werter, Wiebke; Rueck, Angelika C.; Steiner, Rudolf W.; Keckstein, J.

    1994-07-01

    As a new treatment model for endometriosis, photodynamic therapy was applied to endometriotic and endometrial cultures. It could be demonstrated that both endometrial components (epithelium and stroma) were present in the cultures, proved by immunocytology and electron microscopy. No major differences were seen between endometriotic and endometrial cells. The cultures were treated by HpD-sensitized PDT. Incubation time was 24 h and concentrations of 5 and 10 (mu) g/ml were used. Irradiation was performed by an argon-pumped dye laser at 630 nm with a power density of 80 mW/cm2. Evaluation both morphologically and by trypan blue exclusion test, was effected 24 h after irradiation. Toxicity in endometriotic and endometrial cultures was practically identical. Stroma cells were more sensitive to photodynamic treatment than epithelial cells. Complete stromal cell destruction was reached at 15 J/cm2, whereas epithelial cells showed 100 lethality at 40 J/cm2 (10(mu) g/ml HpD). These and subsequent results demonstrate that the sensitivity of stromal cells was about seven times higher than that of epithelial cells.

  5. Epigenetically Enhanced Photodynamic Therapy (ePDT) is Superior to Conventional Photodynamic Therapy for Inducing Apoptosis in Cutaneous T-Cell Lymphoma.

    PubMed

    Salva, Katrin Agnes; Wood, Gary S

    2015-11-01

    Conventional photodynamic therapy with aminolevulinate (ALA-PDT) selectively induces apoptosis in diseased cells and is highly effective for treating actinic keratoses. However, similar results are achieved only in a subset of patients with cutaneous T-cell lymphoma (CTCL). Our previous work shows that the apoptotic resistance of CTCL correlates with low expression of death receptors like Fas cell surface death receptor (FAS), and that methotrexate upregulates FAS by inhibiting the methylation of its promoter, acting as an epigenetic derepressor that restores the susceptibility of FAS-low CTCL to caspase-8-mediated apoptosis. Here, we demonstrate that methotrexate increases the response of CTCL to ALA-PDT, a concept we refer to as epigenetically enhanced PDT (ePDT). Multiple CTCL cell lines were subjected to conventional PDT versus ePDT. Apoptotic biomarkers were analyzed in situ with multispectral imaging analysis of immunostained cells, a method that is quantitative and 5× more sensitive than standard immunohistology for antigen detection. Compared to conventional PDT or methotrexate alone, ePDT led to significantly greater cell death in all CTCL cell lines tested by inducing greater activation of caspase-8-mediated extrinsic apoptosis. Upregulation of FAS and/or tumor necrosis factor-related apoptosis-inducing ligand pathway components was observed in different CTCL cell lines. These findings provide a rationale for clinical trials of ePDT for CTCL. PMID:26302991

  6. The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

    PubMed Central

    Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

    2013-01-01

    Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

  7. The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment.

    PubMed

    Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

    2013-01-01

    Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

  8. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

    PubMed

    Mathew, Aju; Davidson, Nancy E

    2015-11-01

    Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. PMID:26255743

  9. Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis

    PubMed Central

    Tang, Kai; Si, Jun-Kang; Guo, Da-Dong; Cui, Yan; Du, Yu-Xiang; Pan, Xue-Mei; Bi, Hong-Sheng

    2015-01-01

    AIM To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV). METHODS A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis. RESULTS Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P?0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study. CONCLUSION IVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV. PMID:26558226

  10. The simulation of light distribution in photodynamic therapy for port wine stains

    NASA Astrophysics Data System (ADS)

    Zhang, Shi-Yu; Hu, Xiao-Ming; Zhou, Ya

    2014-11-01

    Photodynamic Therapy is regarded as the best treatment for port wine stains, which has the main adverse effect of various degrees of pain (mild to moderate) during the illumination. Though the cooling and cold water have been used to reduce such pain, there is still no scientific evidence for these relief. In this paper, a realistic skin model is built to simulate the distribution of light under treatment, which helps control the light dose and temperature, and improve the clinical results. Comparing with the general parallel skin model, a curving stratum basale layer is used in this paper, and various blood vessel configurations such as single and multiple vessels with horizontally and vertically oriented, curve vessels, various vessel diameter and various radius of curvature of stratum basale layer are simulated. The results shows a more realistic modeling for the thermal damage and help to relief the pain in the treatment.

  11. Vessel constriction correlated with local singlet oxygen generation during vascular targeted photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Lin, Lisheng; Li, Yirong; Zhang, Jinde; Tan, Zou; Chen, Defu; Xie, Shusen; Gu, Ying; Li, Buhong

    2014-11-01

    In this study, the vessel constriction was measured as a biological indicator of acute vascular response after vascular targeted photodynamic therapy (V-PDT). During V-PDT treatment, the near-infrared (NIR) singlet oxygen (1O2) luminescence at 1270 nm generated in blood vessels in a dorsal skinfold window chamber model in vivo was directly monitored using a custom built high-sensitive NIR imaging system. In order to compare the acute vascular response, various irradiances with the same light dose were utilized for treatments. The obtained results show that the complete arteriole constriction occurred frequently, while some of the larger veins were constricted partially. For the vessels that have significant constriction after V-PDT, our preliminary data suggest that the vasoconstriction in the selected ROIs are roughly correlated with the local cumulative 1O2 luminescence intensities. This study implies that the 1O2 luminescence dosimetry maybe also effective for evaluating V-PDT efficiency.

  12. Fluorescence tissue distribution of methylene blue used for photodynamic therapy of Helicobacter Pylori

    NASA Astrophysics Data System (ADS)

    Millson, Charles E.; Buonaccorsi, Giovanni A.; MacRobert, Alexander J.; Mlkvy, Peter; Bown, Stephen G.

    1995-03-01

    Helicobacter pylori is associated with a wide range of pathologies in the upper gastrointestinal tract. Current treatments employing antibiotics are disappointing, and an endoscopic PDT might offer a better alternative. Methylene blue is a widely known histological dye and has been in use for photodynamic therapy experimentally for some years. A prospective application of MB is photosensitization of Helicobacter pylori, but little is known about its effect with light on normal mucosa of the stomach. We studied the fluorescence microscopy of the stomachs of 3 ferrets which had been sensitized by oral route with three different concentrations of MB 1 hour prior to sacrifice. MB at all doses was seen to concentrate on the surface of the mucosa and shows little deeper penetration. As Helicobacter lie on the superficial mucosa, this study suggests that oral dosing with MB should sensitize these bacteria. These findings are an important preliminary to an in vivo trial of PDT for the treatment of H pylori.

  13. Preparation and optimization of aminolevulinic acid with gold nanoparticles for photothermal and photodynamic therapies applications

    NASA Astrophysics Data System (ADS)

    Gonçalves, Karina de O.; da Silva Cordeiro, Thiago; Silva, Flávia de Oliveira; Samad, Ricardo E.; Vieira Júnior, Nilson D.; Courrol, Lilia C.

    2015-06-01

    The use of gold nanoparticles (AuNps) as the vehicle for 5-Aminolevulinic acid (ALA) delivery for photodynamic and photothermic plasmonic therapies is a promising approach, especially with the recent demonstration that this photosensitizer immobilization on the particle surface improves reactive oxygen species (ROS) formation, increasing its cytotoxicity. Gold nanorods (AuNRs) present an absorption spectrum shifted to 700 nm, within the tissue transparency window, which allows excitation of the nanoparticles situated deeper in the tissues. Here, we describe a new synthesis method that was applied to control the shape of the gold nanoparticles during its synthesis. To obtain ALA:AuNRs, precursor ALA:AuNps were irradiated by ultrashort laser pulses. The variation of the laser parameters such as pulse energy and duration and irradiation time was assessed. The relevant mechanisms are discussed.

  14. Synthesis, characterization and biological evaluation of mixed-ligand ruthenium(II) complexes for photodynamic therapy.

    PubMed

    Huang, Huaiyi; Zhang, Pingyu; Yu, Bole; Jin, Chengzhi; Ji, Liangnian; Chao, Hui

    2015-10-21

    This study investigated the photodynamic therapy (PDT) and anticancer activity of mixed ligand Ru(ii) terpyridyl complexes (Ru1-Ru3). The photophysical and photochemical properties, hydrophobic properties, DNA binding and DNA transcription inhibition abilities, cell uptake efficiency, cellular localization and photo-cytotoxicity were investigated. Ru1-Ru3 exhibited red luminescence between 670-710 nm and functioned as photo-sensitizers (PSs) by generating both singlet oxygen and radical ions. Without light activation, Ru1-Ru3 were located at the cytoplasm and were nontoxic to cells. However, upon light activation, Ru1-Ru3 exhibited significant photocytotoxicity. After PDT treatment, mitochondria alteration and nuclear membrane disruption occurred, which resulted in relocalization of the complexes from the cytoplasm to the nucleus. Moreover, high cellular oxidative stress caused cell necrocytosis after PDT treatment. PMID:26387554

  15. The microfluidic system for studies of carcinoma and normal cells interactions after photodynamic therapy (PDT) procedures.

    PubMed

    Jedrych, Elzbieta; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew

    2011-12-01

    This study reports on the use of a microsystem for evaluation of photodynamic therapy (PDT) procedures on the "mixed" (carcinoma-normal) cultures. Balb/3T3 (normal mouse embryo) and A549 (human lung carcinoma) cells were tested in separated and "mixed" cultures. Interactions and migration of cells cultured together were observed. The PDT procedures were examined in the hybrid (PDMS/glass) microsystem which contains cell culture microchambers integrated with network of microchannels. We investigated that the number of dead cells after PDT procedures is dependent on the kind of cell culture. Moreover, the influence of the carcinoma cells on the viability of normal cells in the "mixed" culture was observed. PMID:22662052

  16. Strategy for tuning the photophysical properties of photosensitizers for use in photodynamic therapy.

    PubMed

    Siraj, Noureen; Kolic, Paulina E; Regmi, Bishnu P; Warner, Isiah M

    2015-10-01

    A novel approach for tuning spectral properties, as well as minimizing aggregation, in zinc porphyrin and zinc phthalocyanine-based compounds is presented. Particular emphasis is placed on use of these compounds as photosensitizers in photodynamic therapy (PDT). To accomplish this aim, a bulky hydrophobic cation, trihexyltetradecylphosphonium, is paired with anionic porphyrin and phthalocyanine dyes to produce a group of uniform materials based on organic salts (GUMBOS) that absorb at longer wavelengths with high molar absorptivity and high photostability. Nanoparticles derived from these GUMBOS possess positively charged surfaces with high zeta potential values, which are highly desirable for PDT. Upon irradiation at longer wavelengths, these GUMBOS produced singlet oxygen with greater efficiency as compared to the respective parent dyes. PMID:26288164

  17. Photodynamic therapy via FRET following bioorthogonal click reaction in cancer cells.

    PubMed

    Bio, Moses; Rajaputra, Pallavi; You, Youngjae

    2016-01-01

    Longer wavelength light (650-800nm) is desired to treat large tumors in photodynamic therapy (PDT). However, shorter wavelength light is needed in PDT for thin tumors, not to cause undesirable local side effects. We proposed a strategy for stepwise optical imaging and PDT using a bioorthogonal click chemistry and fluorescence resonance energy transfer (FRET). We prepared azidyl rhodamine (Rh-N3, clickable FD) and cyclooctynyl phthalocyanine [Pc-(DIBAC), clickable PS], with which, here, we demonstrate that the non-catalytic click chemistry is rapid and efficient in cancer cells and FRET from a fluorescence dye (FD) to a photosensitizer (PS) is sufficient to generate enough singlet oxygen killing cancer cells by using shorter wavelength light. PMID:26584884

  18. Development and Evaluation of Nanoemulsions Containing Phthalocyanines for Use in Photodynamic Cancer Therapy.

    PubMed

    Senna, Juliana P; Ricci-Júnior, Eduardo; Mansur, Claudia R E

    2015-06-01

    This work reports the development of oil in water (o/w) nanoemulsions containing poly(ethylene oxide)-poly(propylene oxide) block copolymer surfactant for the formulation of a delivery system for endovenous zinc and chloroaluminum phthalocyanines. A solubility study suggested clove oil and its combination with ethanol as the best candidates for the oil phase composition. The nanoemulsions were obtained using a high-pressure homogenizer and analyzed for droplet size to determine their short- and long-term stability. Formulations containing 7 and 10% oil phase and 12% surfactant presented higher stability and allowed the incorporation of a bigger amount of phthalocyanines in the formulation. Rheological analyses showed the prevailing Newtonian behavior of the nanoemulsions. Studies of toxicity and phototoxicity determined that the nanoemulsions produced were capable of inhibiting the growth of adenocarcinoma tumor cells. The nanoemulsions proved to be a good alternative for use in photodynamic therapy. PMID:26369031

  19. Light dosimetry for photodynamic therapy of superficial tumors in the bladder

    NASA Astrophysics Data System (ADS)

    Beyer, Wolfgang; Pongratz, T.; Hofstetter, Alfons G.; Jocham, Dieter; Unsoeld, Eberhard

    1994-03-01

    Photodynamic therapy (PDT) of tumors in the urinary bladder requires a homogeneous light distribution on the whole organ wall. The light applicator recently developed consists of a catheter-supported isotropic emitter and a concentric outer balloon, which guarantees a centric position. For dosimetry a detector fiber with conical end is axially placed half way between center and bladder outlet. It detects the light backscattered from the bladder wall. It has been tested by means of a bladder phantom model with variable backscattering properties. To study the limits of this irradiation and dosimetry concept in case of nonspherical bladder shapes the light distributions in hollow ellipsoids with backscattering surface have been investigated by computer simulation. It shows that the ratio of the largest to the smallest fluence rate and the ratio of the largest to the smallest diameter of the bladder are nearly equal.

  20. Selenorhodamine photosensitizers with the Texas-red core for photodynamic therapy of cancer cells.

    PubMed

    Kryman, Mark W; Davies, Kellie S; Linder, Michelle K; Ohulchanskyy, Tymish Y; Detty, Michael R

    2015-08-01

    We examined two selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenoxanthylium analogue of the Texas-red core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp)-expressing Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 cells. Both compounds were extremely effective photosensitizers with values of EC50 ? 4 × 10(-8)M toward Colo-26 cells with 1.0 J cm(-2) laser light delivered at 630 ± 2 nm. PMID:26105712

  1. Modeling laser irradiation conditions for mucosal tissues in antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Astaf'eva, L. G.; Plavskii, V. Yu.

    2012-05-01

    We use computer modeling to analzye empirically selected conditions for antimicrobial photodynamic therapy of mucosal tissues. We calculate the optical and thermal fields for experimental conditions for low-intensity (cold) laser irradiation used in treatment of lesions in mucosal tissues stained by methylene blue: ? = 670 nm, power density 150-300 mW/cm2, doses 9-18 J/cm2; ? = 632.8 nm, 15 mW/cm2, dose 4.5 J/cm2. For numerical estimates, we used the optical characteristics of methylene blue and three layers of mucosal tissues at the laser radiation wavelengths, and also the thermal characteristics of the tissues. The experimental conditions were optimized using the ratio of the tissue penetration depth for the absorbed optical energy and the penetration depth of methylene blue into the lesion, while maintaining safe tissue heating temperatures.

  2. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  3. An alternative model for photodynamic therapy of cancers: Hot-band absorption

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Chen, Jiyao

    2013-12-01

    The sulfonated aluminum phthalocyanine (AlPcS), a photosensitizer for photodynamic cancer therapy (PDT), has an absorption tail in the near-infrared region (700-900 nm) which is so-called hot band absorption (HBA). With the HBA of 800 nm, the up-conversion excitation of AlPcS was achieved followed by the anti-Stocks emission (688 nm band) and singlet oxygen production. The HBA PDT of AlPcS seriously damaged the KB and HeLa cancer cells, with a typical light dose dependent mode. Particularly, the in vitro experiments with the AlPcS shielding solutions further showed that the HBA PDT can overcome a self-shielding effect benefiting the PDT applications.

  4. Photodynamic therapy as a new approach in vulvovaginal candidiasis in murine model

    NASA Astrophysics Data System (ADS)

    Santi, Maria E.; Lopes, Rubia G.; Prates, Renato A.; Sousa, Aline; Ferreira, Luis R.; Fernandes, Adjaci U.; Bussadori, Sandra K.; Deana, Alessandro M.

    2015-02-01

    Vulvovaginal candidiasis is a common cause of vaginal infections. This study investigates the efficiency of antimicrobial photodynamic therapy (aPDT) against yeast cells in mice. Methylene blue (MB), malachite green (MG), and a special designed protoporphirin (PpNetNI) were used as photosensitizers. Female BALB-c mice were infected with Candida albicans ATCC 90028. PDT was applied with two different light sources, intravaginal and transabdominal. Vaginal washes were performed and cultivated for microbial quantification. Antimicrobial PDT was able to decrease microbial content with MB and PpNetNI (p<0.05), it was not effective, however, with MG photosensitizer. The results of this study demonstrate that aPDT may be a viable alternative treatment for vaginal candidiasis.

  5. Review of dermatology use of 5-aminolevulinic acid photodynamic therapy in China from 1997 to 2013

    NASA Astrophysics Data System (ADS)

    Wang, Peiru; Zhang, Guolong; Wang, Xiuli

    2015-07-01

    The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.

  6. Improved low-power semiconductor diode lasers for photodynamic therapy in veterinary medicine

    NASA Astrophysics Data System (ADS)

    Lee, Susanne M.; Mueller, Eduard K.; Van de Workeen, Brian C.; Mueller, Otward M.

    2001-05-01

    Cryogenically cooling semiconductor diode lasers provides higher power output, longer device lifetime, and greater monochromaticity. While these effects are well known, such improvements have not been quantified, and thus cryogenically operated semiconductor lasers have not been utilized in photodynamic therapy (PDT). We report quantification of these results from laser power meter and photospectrometer data. The emission wavelengths of these low power multiple quantum well semiconductor lasers were found to decrease and become more monochromatic with decreasing temperature. Significant power output improvements also were obtained at cryogenic temperatures. In addition, the threshold current, i.e. the current at which lasing begins, decreased with decreasing temperature. This lower threshold current combined with the increased power output produced dramatically higher device efficiencies. It is proposed that cryogenic operation of semiconductor diode lasers will reduce the number of devices needed to produce the requisite output for many veterinary and medical applications, permitting significant cost reductions.

  7. Immunoregulatory Cell Depletion Improves the Efficacy of Photodynamic Therapy-Generated Cancer Vaccines

    PubMed Central

    Korbelik, Mladen; Banáth, Judit; Saw, Kyi Min

    2015-01-01

    Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine’s effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine’s effectiveness. PMID:26569233

  8. Immunoregulatory Cell Depletion Improves the Efficacy of Photodynamic Therapy-Generated Cancer Vaccines.

    PubMed

    Korbelik, Mladen; Banáth, Judit; Saw, Kyi Min

    2015-01-01

    Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine's effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine's effectiveness. PMID:26569233

  9. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

    PubMed Central

    Unterweger, Harald; Subatzus, Daniel; Tietze, Rainer; Janko, Christina; Poettler, Marina; Stiegelschmitt, Alfons; Schuster, Matthias; Maake, Caroline; Boccaccini, Aldo R; Alexiou, Christoph

    2015-01-01

    Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ? potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs’ targeting abilities with hypericin’s phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer. PMID:26648714

  10. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.

    PubMed

    Unterweger, Harald; Subatzus, Daniel; Tietze, Rainer; Janko, Christina; Poettler, Marina; Stiegelschmitt, Alfons; Schuster, Matthias; Maake, Caroline; Boccaccini, Aldo R; Alexiou, Christoph

    2015-01-01

    Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55-85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5-5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ? potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs' targeting abilities with hypericin's phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer. PMID:26648714

  11. Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Davidson, Sean R. H.; Weersink, Robert A.; Haider, Masoom A.; Gertner, Mark R.; Bogaards, Arjen; Giewercer, David; Scherz, Avigdor; Sherar, Michael D.; Elhilali, Mostafa; Chin, Joseph L.; Trachtenberg, John; Wilson, Brian C.

    2009-04-01

    With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately ±2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D90, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm-2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm-2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

  12. Macular sensitivity after half-dose verteporfin photodynamic therapy in central serous chorioretinopathy

    PubMed Central

    Sanguansak, Thuss; Pitujaturont, Prapapan; Yospaiboon, Yosanan; Sinawat, Suthasinee; Ratanapakorn, Tanapat; Bhoomibunchoo, Chavakij

    2015-01-01

    Objective To study the macular sensitivity after half-dose verteporfin photodynamic therapy in patients with resolved central serous chorioretinopathy using the automated static perimeter. Methods Prospective consecutive case study of 24 patients with resolved central serous chorioretinopathy was performed. The macular sensitivity was measured using a conventional automated static perimeter with the Swedish interactive threshold algorithm 10-2 and foveal threshold. Best corrected visual acuity, intraocular pressure, fundus examination, macular thickness, and volume were also examined. The mean macular sensitivities of the affected eyes and their normal fellow eyes were calculated and compared. P<0.05 was considered statistically significant. Results The mean macular sensitivities of the affected eyes were lower than the normal fellow eyes with a statistically significant difference in all areas of the study (P<0.05). Best corrected visual acuity improved significantly from pretreatment (0.26±0.3 logMAR) to posttreatment (0.075±0.15 logMAR, P<0.05). Macular thicknesses in affected eyes were 230.66±67.34 ?m and in the normal eyes were 238.33±92.26 ?m (P=0.68). Macular volumes in affected eyes were 8.77±0.49 and in the normal eyes were 8.70±0.50 (P=0.60). These findings were not statistically significant. Conclusion Eyes with resolved central serous chorioretinopathy after half-dose verteporfin photodynamic therapy had lower macular sensitivity than normal fellow eyes. These findings agreed well with the previous microperimetric studies. The conventional automated static perimeter can also be used when a microperimeter is not available. PMID:26664040

  13. Antitumor activity of photodynamic therapy with a chlorin derivative in vitro and in vivo.

    PubMed

    Wang, Lai-Xing; Li, Jian-Wei; Huang, Jian-Yue; Li, Jian-Hong; Zhang, Li-Jun; O'Shea, Donal; Chen, Zhi-Long

    2015-08-01

    Chlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. The aim of the current study is to investigate the PDT therapeutic effects of a novel chlorin-based photosensitizer, meso-tetra[3-(N,N-diethyl)aminomethyl-4-methoxy]phenyl chlorin (TMPC) for gliomas in vitro and in vivo. Physicochemical characteristics of TMPC were recorded by ultraviolet visible spectrophotometer and fluorescence spectrometer. The rate of singlet oxygen generation of TMPC upon photo-excitation was detected by using 1,3-diphenylisobenzofuran (DPBF). The accumulation of TMPC in gliomas U87 MG cells was measured by fluorescence spectrometer. The efficiency of TMPC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The biodistribution and clearance of TMPC were determined by fluorescence measuring. Human gliomas U87 MG tumor-bearing mice model was used to evaluate the antitumor effects of TMPC-PDT. TMPC shows a singlet oxygen generation rate of 0.05 and displays a characteristic long wavelength absorption peak at 653 nm (??=?15,400). The accumulation of TMPC increased with the increase of incubation time. In vitro, PDT using TMPC and laser showed laser dose- and concentration-dependent cytotoxicity to U87 MG cells. In U87 MG tumor-bearing mice, TMPC-PDT significantly reduced the growth of the tumors. Both in vitro and in vivo, TMPC showed little dark toxicity. In vitro and in vivo studies, it found that TMPC has excellent antitumor activities. It suggests that TMPC is a potential photosensitizer of photodynamic therapy for cancer. PMID:25846737

  14. The impact of antimicrobial photodynamic therapy on Streptococcus mutans in an artificial biofilm model

    NASA Astrophysics Data System (ADS)

    Schneider, Martin; Kirfel, Gregor; Krause, Felix; Berthold, Michael; Brede, Olivier; Frentzen, Matthias; Braun, Andreas

    2010-02-01

    The aim of the study was to assess the impact of laser induced antimicrobial photodynamic therapy on the viability of Streptococcus mutans cells employing an aritificial biofilm model. Employing sterile chambered coverglasses, a salivary pellicle layer formation was induced in 19 chambers. Streptococcus mutans cells were inoculated in a sterile culture medium. Using a live/dead bacterial viability kit, bacteria with intact cell membranes stain fluorescent green. Test chambers containing each the pellicle layer and 0.5 ml of the bacterial culture were analyzed using a confocal laser scan microscope within a layer of 10 ?m at intervals of 1 ?m from the pellicle layer. A photosensitizer was added to the test chambers and irradiated with a diode laser (wavelength: 660 nm, output power: 100 mW, Helbo) for 2 min each. Comparing the baseline fluorescence (median: 13.8 [U], min: 3.7, max: 26.2) with the values after adding the photosensitizer (median: 3.7, min: 1.1, max: 9), a dilution caused decrease of fluorescence could be observed (p<0.05). After irradiation of the samples with a diode laser, an additional 48 percent decrease of fluorescence became evident (median: 2.2, min: 0.4, max: 3.4) (p<0.05). Comparing the samples with added photosensitizer but without laser irradiation at different times, no decrease of fluorescence could be measured (p>0.05). The present study indicates that antimicrobial photodynamic therapy can reduce living bacteria within a layer of 10 ?m in an artificial biofilm model. Further studies have to evaluate the maximum biofilm thickness that still allows a toxic effect on microorganisms.

  15. A drug carrier targeting murine uPAR for photodynamic therapy and tumor imaging.

    PubMed

    Zhou, Xiaolei; Zheng, Ke; Li, Rui; Chen, Zhuo; Yuan, Cai; Hu, Ping; Chen, Jincan; Xue, Jinping; Huang, Mingdong

    2015-09-01

    Photodynamic therapy (PDT) has been used as an effective therapeutical modality for tumors. In PDT, a photosensitizer was used to capture the light of specific wavelength, leading to the generation of reactive oxygen species and cytotoxicity surrounding the photosensitizer. Modifications of photosensitizers to enhance tumor specificity are common approaches to increase the efficacy and reduce the side effects of PDT. Previously, we developed a human serum albumin (HSA)-based drug carrier fused with the human amino-terminal fragment (hATF), which binds to a tumor surface marker (urokinase receptor, uPAR). However, hATF-HSA binds to murine uPAR much weaker (79-fold) than to human uPAR, and is not optimal for applications on murine tumor models. In this study, we developed a murine version of the drug carrier (mATF-HSA). A photosensitizer (mono-substituted ?-carboxy phthalocyanine zinc, CPZ) was loaded into this carrier, giving a rather stable macromolecule (mATF-HSA:CPZ) that was shown to bind to murine uPAR in vitro. In addition, we evaluated both the photodynamic therapy efficacy and tumor retention capability of the macromolecule (at a dose of 0.05mg CPZ/kg mouse body weight) on murine hepatoma-22 (H22) tumor bearing mouse model. mATF-HSA:CPZ showed more accumulation in tumors compared to its human counterpart (hATF-HSA:CPZ) measured by quantitative fluorescence molecular tomography (FMT). Besides, mATF-HSA:CPZ exhibited a higher tumor killing efficacy than hATF-HSA:CPZ. Together, the macromolecule mATF-HSA is a promising tumor-specific drug carrier on murine tumor models and is an useful tool to study tumor biology on murine tumor models. PMID:26004218

  16. Spatiotemporally photoradiation-controlled intratumoral depot for combination of brachytherapy and photodynamic therapy for solid tumor.

    PubMed

    Mukerji, Ratul; Schaal, Jeffrey; Li, Xinghai; Bhattacharyya, Jayanta; Asai, Daisuke; Zalutsky, Michael R; Chilkoti, Ashutosh; Liu, Wenge

    2016-02-01

    In an attempt to spatiotemporally control both tumor retention and the coverage of anticancer agents, we developed a photoradiation-controlled intratumoral depot (PRCITD) driven by convection enhanced delivery (CED). This intratumoral depot consists of recombinant elastin-like polypeptide (ELP) containing periodic cysteine residues and is conjugated with a photosensitizer, chlorin-e6 (Ce6) at the N-terminus of the ELP. We hypothesized that this cysteine-containing ELP (cELP) can be readily crosslinked through disulfide bonds upon exposure to oxidative agents, specifically the singlet oxygen produced during photodynamic stimulation. Upon intratumoral injection, CED drives the distribution of the soluble polypeptide freely throughout the tumor interstitium. Formation and retention of the depot was monitored using fluorescence molecular tomography imaging. When imaging shows that the polypeptide has distributed throughout the entire tumor, 660-nm light is applied externally at the tumor site. This photo-radiation wavelength excites Ce6 and generates reactive oxygen species (ROS) in the presence of oxygen. The ROS induce in situ disulfide crosslinking of the cysteine thiols, stabilizing the ELP biopolymer into a stable therapeutic depot. Our results demonstrate that this ELP design effectively forms a hydrogel both in vitro and in vivo. These depots exhibit high stability in subcutaneous tumor xenografts in nude mice and significantly improved intratumoral retention compared to controls without crosslinking, as seen by fluorescent imaging and iodine-125 radiotracer studies. The photodynamic therapy provided by the PRCITD was found to cause significant tumor inhibition in a Ce6 dose dependent manner. Additionally, the combination of PDT and intratumoral radionuclide therapy co-delivered by PRCITD provided a greater antitumor effect than either monotherapy alone. These results suggest that the PRCITD could provide a stable platform for delivering synergistic, anti-cancer drug depots. PMID:26702586

  17. Photodynamic Therapy

    MedlinePLUS

    ... sunlight, but you don’t have stay in dark rooms. Some indoor light is important because it ... sure windows and skylights are fully covered. Bring dark sunglasses, gloves, a wide brimmed hat, long pants, ...

  18. Assessment of Photodynamic Therapy (PDT) in Disinfection of Deeper Dentinal Tubules in a Root Canal System: An In Vitro Study

    PubMed Central

    Bhaskar, Dara John; Agali, Chandan R; Punia, Himanshu; Gupta, Vipul; Singh, Vikas; Kadtane, Safalya; Chandra, Sneha

    2014-01-01

    Context: The success of endodontic treatment therapy depends on how well we eliminate pathogenic microflora from the root canal system as micro organism as the major cause of root canal infection. Conventional root canal treatment can fail if microorganisms cannot be removed sufficiently by thorough cleaning, shaping of root canal. Newer modalities such as photodynamic therapy are being tried now a days for disinfection of root canals. Aim & Objectives: The basic aim of this study was assessment of the antimicrobial efficacy of Photodynamic Therapy in deeper dentinal tubules for effective disinfection of root canals using microbiological and scanning electron microscopic examination in vitro. Materials and Methods: The study was conducted at Teerthanker Mahaveer Dental College & Research Centre. The teeth required for study was collected from Department of Oral and Maxillofacial Surgery. Only freshly extracted 20 intact, non carious single rooted teeth which were indicated for orthodontic treatment were taken for this study. Statistical analysis was done using Student’s Unpaired t-test were at (p<0.001) was found to be highly significant. Microbiological examination of samples were done and colony forming units were counted to assess the disinfection potential of photodynamic therapy. Scanning electron microscopic examination of samples was done to check penetration of bacteria’s into deeper dentinal tubules. Results: On examination, there was a marked reduction in microbial growth after use of photodynamic therapy. On scanning electron microscopic examination, it was observed that there were less number of bacteria’s in deeper dentinal tubules in case of PDT group as compared to control group. Conclusion: The results of the present study indicate that PDT can be effectively used during antimicrobial procedures along with conventional disinfection procedure for sterilization of root canals. PMID:25584321

  19. Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer

    PubMed Central

    Juzenas, Petras; Chen, Wei; Sun, Ya-Ping; Coelho, Manuel Alvaro Neto; Generalov, Roman; Generalova, Natalia; Christensen, Ingeborg Lie

    2009-01-01

    Semiconductor quantum dots and nanoparticles composed of metals, lipids or polymers have emerged with promising applications for early detection and therapy of cancer. Quantum dots with unique optical properties are commonly composed of cadmium contained semiconductors. Cadmium is potentially hazardous, and toxicity of such quantum dots to living cells, and humans, is not yet systematically investigated. Therefore, search for less toxic materials with similar targeting and optical properties is of further interest. Whereas, the investigation of luminescence nanoparticles as light sources for cancer therapy is very interesting. Despite advances in neurosurgery and radiotherapy the prognosis for patients with malignant gliomas has changed little for the last decades. Cancer treatment requires high accuracy in delivering ionizing radiation to reduce toxicity to surrounding tissues. Recently some research has been focused in developing photosensitizing quantum dots for production of radicals upon absorption of visible light. In spite of the fact that visible light is safe, this approach is suitable to treat only superficial tumours. Ionizing radiation (X-rays and gamma rays) penetrate much deeper thus offering a big advantage in treating patients with tumours in internal organs. Such concept of using quantum dots and nanoparticles to yield electrons and radicals in photodynamic and radiation therapies as well their combination is reviewed in this article. PMID:18840487

  20. Synergistic effect of photodynamic therapy and cisplatin: a novel approach for cervical cancer.

    PubMed

    de Freitas, Laura Marise; Soares, Christiane Pienna; Fontana, Carla Raquel

    2014-11-01

    Cervical cancer is a neoplasia primarily caused by Human papillomavirus (HPV) infection. Current treatment modalities involve cisplatin, a potent chemotherapeutic agent with severe adverse effects. Photodynamic therapy (PDT) is a promising modality for the treatment of cancer and infections, which has been associated with innovative therapeutic approaches, especially for the treatment of neoplasias. This study aimed to investigate the anticancer potential of PDT mediated by methylene blue (MB) or Photogem (PG) individually and combined with cisplatin in vitro. SiHa, C-33 A and HaCaT cells were incubated with MB, PG and/or cisplatin and received no further treatment or were irradiated with a 630 or a 660 nm LED light source at energy densities varying according to the photosensitizer (PS). The MTT assay was employed to assess cell viability. Both PS were effective in reducing cell viability with the cytotoxicity being dependent on the light dose. When compared to PDT groups, cisplatin was less effective. The cell viability of the combined therapy groups was significantly lower compared to monotherapies. The sequence of treatments (PDT+cisplatin/cisplatin+PDT) was important and had different results when varying the PS, but combination therapy resulted in an enhanced anticancer effect regardless of treatment protocol. PMID:25240426

  1. Red-emitting upconverting nanoparticles for photodynamic therapy in cancer cells under near-infrared excitation.

    PubMed

    Tian, Gan; Ren, Wenlu; Yan, Liang; Jian, Shan; Gu, Zhanjun; Zhou, Liangjun; Jin, Shan; Yin, Wenyan; Li, Shoujian; Zhao, Yuliang

    2013-06-10

    Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red-emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha-cyclodextrin-modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near-infrared excitation. Moreover, two different kinds of drugs are co-loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)-induced chemotherapy and Ce6-triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro. PMID:23239556

  2. Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

    PubMed Central

    Reginato, Eleonora; Wolf, Peter; Hamblin, Michael R

    2014-01-01

    Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment. PMID:25364655

  3. Hematoporphyrin-mediated photodynamic therapy for treatment of head and neck cancer: clinical update 1996

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1996-04-01

    From 1983 to 1996 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 55 of 56 patients treated with hematoporphyrin-derivative or PHOTOFRIN-mediated photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial 'condemned mucosa' or 'field cancerization' of the oral cavity and larynx (7 cases); (2) Stage III/IV head and neck cancer (25 cases); (3) mucocutaneous AIDS-associated Kaposi's sarcoma of the upper aerodigestive tract and non AIDS-related Kaposi's sarcoma of the lower extremity (15 cases); (4) recurrent laryngotracheal papillomatosis (3 cases); (5) severe dysplasia/adenocarcinoma or squamous cell carcinoma in situ in Barrett's esophagus (4 cases); (6) partial or completely obstructing terminal esophageal cancer (9 cases). At the time of this report, HPD-PDT produced complete responses in 24 patients (follow up 6 months to 9 years) with 'field cancerization' (CIS, T1N0M0) of the oral cavity and larynx (6 cases), adenocarcinoma in situ in Barrett's esophagus (3 cases), mucocutaneous Kaposi's sarcoma (12 cases), obstructing esophageal carcinoma (1 case), and stage IV squamous cell carcinoma of the nasopharynx (1 case), and radiation therapy or solar-induced basal cell/squamous cell carcinomas (2 cases). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck cancer are reviewed in this article.

  4. Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Spring, Bryan; Mai, Zhiming; Rai, Prakash; Chang, Sung; Hasan, Tayyaba

    2010-02-01

    Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the "right place at the right time". This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

  5. In vivo measurement of fluorescence emission in the human prostate during photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Stripp, Diana; Malkowicz, S. B.; Whittington, Richard; Miles, Jeremy; Glatstein, Eli; Hahn, Stephen M.

    2005-04-01

    Among the challenges to the clinical implementation of photodynamic therapy (PDT) is the delivery of a uniform photodynamic dose to induce uniform damage to the target tissue. As the photodynamic dose depends on both the local sensitizer concentration and the local fluence rate of treatment light, knowledge of both of these factors is essential to the delivery of uniform dose. In this paper, we investigate the distribution and kinetics of the photosensitizer motexafin lutetium (MLu, Lutrin) as revealed by its fluorescence emission. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing fibers (CDF"s) inserted into the prostate though clear catheters. For planning and treatment purposes, the prostate is divided into 4 quadrants. We use one catheter in each quadrant to place an optical fiber-based fluorescence probe into the prostate. This fiber is terminated in a beveled tip, allowing it to deliver and collect light perpendicular to the fiber axis. Excitation light is provided by a 465 nm light emitting diode (LED) source coupled to a dichroic beamsplitter, which passes the collected fluorescence emission to a CCD spectrograph. Spectra are obtained before and after PDT treatment in each quadrant of the prostate and are analyzed via a linear fitting algorithm to separate the MLu fluorescence from the background fluorescence originating in the plastic catheter. A computer-controlled step motor allows the excitation/detection fiber to be moved along the catheter, building up a linear profile of the fluorescence emission spectrum of the tissue as a function of position. We have analyzed spectral fluorescence profiles obtained in 4 patients before and after MLu-mediated PDT. We find significant variation both within individual prostates and among patients. Within a single quadrant, we have observed the fluorescence signal to change by as much as a factor of 3 over a distance of 2 cm. Comparisons of pre- and post-PDT spectra allow a quantification treatment-induced photobleaching. Like the drug distribution, the extent of photobleaching varies widely among patients. In two cases, we observed bleaching of approximately 50% of the drug, while others exhibited negligible photobleaching.

  6. Reversibility of Left Ventricle Longitudinal Strain Alterations Induced by Adjuvant Therapy in Early Breast Cancer Patients.

    PubMed

    Mele, Donato; Malagutti, Patrizia; Indelli, Monica; Ferrari, Lucia; Casadei, Francesca; Da Ros, Lucia; Pollina, Alberto; Fiorencis, Andrea; Frassoldati, Antonio; Ferrari, Roberto

    2016-01-01

    Left ventricular ejection fraction (LV-EF), despite its high feasibility, is not sensitive enough to detect early and subtle LV systolic dysfunction during oncologic treatments. Therefore, we used systolic global longitudinal strain (GLS) by speckle tracking echocardiography to verify whether early LV systolic dysfunction induced by adjuvant therapy in early breast cancer patients at low risk for cardiotoxicity can be reversed. Thirty patients (aged 53 ± 11 y) with no previous cardiac and oncologic disease who were receiving adjuvant trastuzumab and taxane (group HER2+, n = 15) or taxane only (group HER2-, n = 15), after treatment with anthracyclines, were studied. LV-EF and GLS were measured at baseline, after anthracyclines (end of week 7 or 8), short term after trastuzumab and/or taxane (end of week 18) and after completion of therapy. Significant LV systolic dysfunction was defined as a relative reduction in GLS of >10% with respect to baseline values. Mean and individual LV-EFs did not change significantly during the oncologic treatment and after completion of therapy, although GLS varied significantly. In particular, during the course of therapy, four patients in the trastuzumab-docetaxel HER2+ subgroup and two patients in the taxane HER2- subgroup had a relative decrease (>10%) in GLS. However, after the end of adjuvant treatment, strain modification was fully or partially reversible. Speckle tracking echocardiography is more sensitive than LV-EF in recognizing subtle myocardial impairment during adjuvant chemotherapy. However, in patients at low risk for cardiotoxicity, these alterations may be reversible and not associated with clinically significant cardiotoxicity or late development of decreased LV-EF. PMID:26603736

  7. Lisofylline as an adjuvant to high dose cytotoxic therapy.

    PubMed

    Teicher, B; Kakeji, Y; Northey, D

    1997-08-01

    Lisofylline, a dimethylxanthine derivative, has been shown to block the induction of hematopoietic growth inhibitors produced in response to cytotoxic anticancer therapy. In the current study, mice bearing established EMT-6 mammary carcinoma were treated with high dose cyclophosphamide, melphalan, BCNU, 5-fluorouracil or with total body radiation alone or with peripheral blood cells. The effect of lisofylline and/or G-CSF on leukocyte recovery was examined. Lisofylline was as effective as G-CSF in accelerating the recovery of white blood cells and granulocytes after treatment with high dose chemotherapy or total body radiation. Lisofylline alone or along with G-CSF was effective in protecting animals from the weight loss caused by high dose melphalan but not from weight loss caused by other cytotoxic therapies. Administration of lisofylline did not alter the killing of bone marrow CFU-GM by single doses of cyclophosphamide, melphalan or BCNU. However, administration of lisofylline increased the killing of EMT-6 tumor cells taken from the same animals. Administration of lisofylline had no effect on EMT-6 tumor growth. However, treatment with lisofylline along with high dose cyclophosphamide: melphalan, BCNU or 5-fluorouracil significantly increased the tumor growth delay produced by these agents. Overall, in the high dose therapy/EMT-6 mammary carcinoma model, lisofylline selectively enhanced hematopoietic recovery and increased tumor response to cytotoxic therapy. PMID:21528210

  8. Preparation of fluorescent mesoporous hollow silica-fullerene nanoparticles via selective etching for combined chemotherapy and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Yang, Yannan; Yu, Meihua; Song, Hao; Wang, Yue; Yu, Chengzhong

    2015-07-01

    Well-dispersed mesoporous hollow silica-fullerene nanoparticles with particle sizes of ~50 nm have been successfully prepared by incorporating fullerene molecules into the silica framework followed by a selective etching method. The fabricated fluorescent silica-fullerene composite with high porosity demonstrates excellent performance in combined chemo/photodynamic therapy.Well-dispersed mesoporous hollow silica-fullerene nanoparticles with particle sizes of ~50 nm have been successfully prepared by incorporating fullerene molecules into the silica framework followed by a selective etching method. The fabricated fluorescent silica-fullerene composite with high porosity demonstrates excellent performance in combined chemo/photodynamic therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02769a

  9. Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells

    NASA Astrophysics Data System (ADS)

    Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

    2015-02-01

    This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm2 at 5 J/cm2 about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation.

  10. Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy

    PubMed Central

    2015-01-01

    A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal ?-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP–PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics. PMID:25291544

  11. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group.

    PubMed

    Mackey, J R; Clemons, M; Côté, M A; Delgado, D; Dent, S; Paterson, A; Provencher, L; Sawyer, M B; Verma, S

    2008-01-01

    Trastuzumab has been shown to be an effective therapy for women with breast cancer that overexpresses the human epidermal growth factor receptor 2 (her2) protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was observed in women treated with trastuzumab and chemotherapy. The incidence and severity of cardiac dysfunction was greatest among patients who received trastuzumab in combination with anthracycline-based therapy. Those findings influenced the design of subsequent trastuzumab trials to include prospective evaluations of cardiac effects and protocols for cardiac monitoring and management. The risk of cardiotoxicity has also driven efforts to develop non-anthracycline-based regimens for women with her2-positive breast cancers.With the increasing use of trastuzumab, particularly in the curative adjuvant setting, the need for a rational approach to the treatment and cardiac management of the relevant patient population is clear. The mandate of the Canadian Trastuzumab Working Group was to formulate recommendations, based on available data, for the assessment and management of cardiac complications during adjuvant trastuzumab therapy. The panel formulated recommendations in four areas: Risk factors for cardiotoxicity, Effects of various regimens, Monitoring, Management. The recommendations published here are expected to evolve as more data become available and experience with trastuzumab in the adjuvant setting grows. PMID:18317582

  12. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group

    PubMed Central

    Mackey, J.R.; Clemons, M.; Côté, M.A.; Delgado, D.; Dent, S.; Paterson, A.; Provencher, L.; Sawyer, M.B.; Verma, S.

    2008-01-01

    Trastuzumab has been shown to be an effective therapy for women with breast cancer that overexpresses the human epidermal growth factor receptor 2 (her2) protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was observed in women treated with trastuzumab and chemotherapy. The incidence and severity of cardiac dysfunction was greatest among patients who received trastuzumab in combination with anthracycline-based therapy. Those findings influenced the design of subsequent trastuzumab trials to include prospective evaluations of cardiac effects and protocols for cardiac monitoring and management. The risk of cardiotoxicity has also driven efforts to develop non-anthracycline-based regimens for women with her2-positive breast cancers. With the increasing use of trastuzumab, particularly in the curative adjuvant setting, the need for a rational approach to the treatment and cardiac management of the relevant patient population is clear. The mandate of the Canadian Trastuzumab Working Group was to formulate recommendations, based on available data, for the assessment and management of cardiac complications during adjuvant trastuzumab therapy. The panel formulated recommendations in four areas: Risk factors for cardiotoxicityEffects of various regimensMonitoringManagement The recommendations published here are expected to evolve as more data become available and experience with trastuzumab in the adjuvant setting grows. PMID:18317582

  13. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  14. Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

    PubMed Central

    Boyle, John; Czito, Brian; Willett, Christopher

    2015-01-01

    Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

  15. Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

    PubMed

    Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

    2015-08-01

    Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

  16. Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

    PubMed

    Yu, Jiashing; Hsu, Che-Hao; Huang, Chih-Chia; Chang, Po-Yang

    2015-01-14

    Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development. PMID:25494339

  17. Single LED-based device to perform widefield fluorescence imaging and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Grecco, Clovis; Buzzá, Hilde H.; Stringasci, Mirian D.; Andrade, Cintia T.; Vollet-Filho, Jose D.; Pratavieira, Sebastião.; Zanchin, Anderson L.; Tuboy, Aparecida M.; Bagnato, Vanderlei S.

    2015-06-01

    Photodynamic therapy (PDT) is a treatment modality that can be indicated for several cancer types and pre-cancer lesions. One of the main applications of PDT is the treatment of superficial skin lesions such as basal cell carcinoma, Bowen's disease and actinic keratosis. Three elements are necessary in PDT, a photosensitizer (PS); light at specific wavelength to be absorbed by the PS, and molecular oxygen. A typical PS used for skin lesion is protoporphyrin IX (PpIX), which is an intrinsic PS; its production is stimulated by a pro-drug, such as 5-aminolevulinic acid (ALA). Before starting a treatment, it is very important to follow up the PpIX production (to ensure that enough PS was produced prior to a PDT application) and, during a PDT session, to monitor its photodegradation (as it is evidence of the photodynamic effect taking place). The aim of this paper is to present a unique device, LINCE (MMOptics - São Carlos, Brazil), that brings together two probes that can, respectively, allow for fluorescence imaging and work as a light source for PDT treatment. The fluorescence probe of the system is optically based on 400 nm LED (light emitting diodes) arrays that allow observing the fluorescence emission over 450 nm. The PDT illumination probe options are constituted of 630 nm LED arrays for small areas and, for large areas, of both 630 nm and 450 nm LED arrays. Joining both functions at the same device makes PDT treatment simpler, properly monitorable and, hence, more clinically feasible. LINCE has been used in almost 1000 PDT treatments of superficial skin lesions in Brazil, with 88.4% of clearance of superficial BCC.

  18. Photodynamic therapy for inactivating endodontic bacterial biofilms and effect of tissue inhibitors on antibacterial efficacy

    NASA Astrophysics Data System (ADS)

    Shrestha, Annie; Kishen, Anil

    Complex nature of bacterial cell membrane and structure of biofilm has challenged the efficacy of antimicrobial photodynamic therapy (APDT) to achieve effective disinfection of infected root canals. In addition, tissue-inhibitors present inside the root canals are known to affect APDT activity. This study was aimed to assess the effect of APDT on bacterial biofilms and evaluate the effect of tissue-inhibitors on the APDT. Rose-bengal (RB) and methylene-blue (MB) were tested on Enterococcus faecalis (gram-positive) and Pseudomonas aeruginosa (gram-negative) biofilms. In vitro 7- day old biofilms were sensitized with RB and MB, and photodynamically activated with 20-60 J/cm2. Photosensitizers were pre-treated with different tissue-inhibitors (dentin, dentin-matrix, pulp tissue, bacterial lipopolysaccharides (LPS), and bovine serum albumin (BSA)) and tested for antibacterial effect of APDT. Microbiological culture based analysis was used to analyze the cell viability, while Laser Scanning Confocal Microscopy (LSCM) was used to examine the structure of biofilm. Photoactivation resulted in significant reduction of bacterial biofilms with RB and MB. The structure of biofilm under LSCM was found to be disrupted with reduced biofilm thickness. Complete biofilm elimination could not be achieved with both tested photosensitizers. APDT effect using MB and RB was inhibited in a decreasing order by dentin-matrix, BSA, pulp, dentin and LPS (P< 0.05). Both strains of bacterial biofilms resisted complete elimination after APDT and the tissue inhibitors existing within the root canal reduced the antibacterial activity at varying degrees. Further research is required to enhance the antibacterial efficacy of APDT in an endodontic environment.

  19. Three-dimensional cell culturing by magnetic levitation for evaluating efficacy/toxicity of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sabino, Luis G.; Menezes, Priscila F. C.; Bagnato, Vanderlei S.; Souza, Glauco; Killian, Thomas C.; Kurachi, Cristina

    2014-03-01

    We used three dimensional cell cultures (3D) based on the magnetic levitation method (MLM) to evaluate cytotoxicity of photodynamic therapy (PDT). First, we decorated Hep G2 and MDA-MB-321 cells with NanoShuttle by introducing it in the media and incubated overnight. Next day, we transferred the cells to a 6-well plate and placed a magnetic driver on the top of the plate to start levitation. We monitored the formation of the 3D cell culture by optical microscopy and after four days, we added the photosensitizer Photogem (PG) in the culture media in concentrations of 50, 25, 12.5, 6.25?g/ml. We incubated them for 24 hours, after that we washed the cultures with PBS and added fresh media. Samples were then illuminated for 600s using a 630nm LED-based device, generating light intensities of 30 mW/cm2 in a total light fluence of 18 J/cm2. Following the illumination, we added fresh media, and 30 hours later, the 3D structures were broken using a pipettor and the cells seeded in 96 well plates, 105 cells per well, with a magnetic drive placed on the bottom of the plate to create cell culture dots. After 24 hours, we used a MTT assay to evaluate PDT cytotoxicity. The PDT effect, evaluated by the half maximal effective concentration (EC50), in MDA-MB-231 cells (EC50 =3.14 ?g/ml) is more aggressive compared to the effect of PDT in Hep G2 cells (EC50 = 7.48 ?g/ml). It suggests that the cell culture structure and its interaction facilitated the PG uptake and consequently elevated the Photodynamic effect for MDA-MB-231.

  20. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

    NASA Astrophysics Data System (ADS)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

    2011-02-01

    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  1. Pharmacology of photosensitizer in rats with metastatic breast cancer: time point determination for photodynamic therapy (PDT) treatment of vertebral metastases

    NASA Astrophysics Data System (ADS)

    Akens, Margarete K.; Yee, Albert J. M.; Lilge, Lothar; Burch, Shane; Whyne, Cari; Wilson, Brian C.; Bisland, Stuart K.

    2005-09-01

    Photodynamic therapy (PDT) as a non-radiative treatment has been applied successfully in various cancers. PDT may be a useful adjunct in the treatment of vertebral metastases. PDT efficacy requires the administration of a photosensitiser drug followed by subsequent drug activation by wavelength specific light. The study purpose was to establish the pharmacokinetic profiles for 2 photosensitisers, BPD-MA and 5-ALA induced PpIX, to determine the optimal drug-light interval for vertebral PDT.

  2. In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

    SciTech Connect

    Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

    2009-01-01

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

  3. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    NASA Astrophysics Data System (ADS)

    de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

    2015-04-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×1013 or 1.50×1013 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

  4. Photodynamic therapy of Pheophorbide a inhibits the proliferation of human breast tumour via both caspase-dependent and -independent apoptotic pathways in in vitro and in vivo models.

    PubMed

    Hoi, Sandy Wan-Heng; Wong, Hoi Ming; Chan, Judy Yuet-Wa; Yue, Grace Gar Lee; Tse, Gary Man-Kit; Law, Bonita Ka-Bo; Fong, Wing Ping; Fung, Kwok Pui

    2012-05-01

    Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)(50) of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5 µm. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer. PMID:22072524

  5. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    SciTech Connect

    Pinkham, Mark B.; Foote, Matthew C.; Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane; Diamantina Institute, Brisbane; University of Queensland, Brisbane ; Burmeister, Elizabeth; Research Centre for Clinical and Community Practice, Griffith University, Brisbane ; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; University of Queensland, Brisbane ; Burmeister, Bryan H.; Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane; University of Queensland, Brisbane

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  6. Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies

    NASA Astrophysics Data System (ADS)

    Yan, Xuefeng; Hu, Hao; Lin, Jing; Jin, Albert J.; Niu, Gang; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

    2015-01-01

    Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT.

  7. The Effect of Iron Ion on the Specificity of Photodynamic Therapy with 5-Aminolevulinic Acid

    PubMed Central

    Hayashi, Maiko; Fukuhara, Hideo; Inoue, Keiji; Shuin, Taro; Hagiya, Yuichiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects. PMID:25822972

  8. Photodynamic therapy of melanoma using new, synthetic porphyrins and phthalocyanines as photosensitisers – a comparative study

    PubMed Central

    BALDEA, IOANA; ION, RODICA-MARIANA; OLTEANU, DIANA ELENA; NENU, IULIANA; TUDOR, DIANA; FILIP, ADRIANA GABRIELA

    2015-01-01

    Melanoma, a cancer that arises from melanocytes, is one of the most unresponsive cancers to known therapies and has a tendency to produce early metastases. Several studies showed encouraging results of the efficacy of photodynamic therapy (PDT) in melanoma, in different experimental settings in vitro and in vivo, as well as several clinical reports. Aims Our study focuses on testing the antimelanoma efficacy of several new, synthetic photosensitisers (PS), from two different chemical classes, respectively four porphyrins and six phthalocyanines. Methods These PS were tested in terms of cell toxicity and phototoxicity against a radial growth phase melanoma cell line (WM35), in vitro. Cells were exposed to different concentrations of the PS for 24h, washed, then irradiatied with red light (630 nm) 75 mJ/cm2 for the porphyrins and 1 J/cm2 for the phthalocyanines. Viability was measured using the MTS method. Results Two of the synthetic porphyrins, TTP and THNP, were active photosensitizers against WM35 melanoma in vitro. Phthalocyanines were effective in producing a dose dependent PDT-induced decrease in viability in a dose-dependent manner. The most efficient was Indium (III) Phthalocyanine chloride, a metal substituted phthalocyanine. Conclusions The most efficient photosensitizers for PDT in melanoma cells were the phthalocyanines in terms of tumor cell photokilling and decreased dark toxicity. PMID:26528068

  9. Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

    2005-01-01

    In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

  10. Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

    SciTech Connect

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2010-01-15

    Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

  11. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections

    PubMed Central

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A.; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-01-01

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O2, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores. PMID:26343645

  12. Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature.

    PubMed

    Kikuchi, Takeshi; Mogi, Makio; Okabe, Iichiro; Okada, Kosuke; Goto, Hisashi; Sasaki, Yasuyuki; Fujimura, Takeki; Fukuda, Mitsuo; Mitani, Akio

    2015-01-01

    Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT) has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy. PMID:26473843

  13. Susceptibility of Candida albicans to photodynamic therapy using methylene blue and toluidine blue as photosensitizing dyes.

    PubMed

    Pupo, Yasmine M; Gomes, Giovana M; Santos, Elizabete B; Chaves, Luzia; Michel, Milton D; Kozlowski, Vitoldo A; Gomes, Osnara M M; Gomes, Joãdo Carlos

    2011-01-01

    The increased resistance of Candida albicans to antibiotic therapy indicates the need for alternative treatments for oral candidiasis. Photodynamic therapy (PDT) has been researched as an alternative tool to inactivate pathogenic microorganisms. It uses a combination of a photosensitizer and a visible light source. This study evaluated the susceptibility of C. albicans to PDT and compared the efficacy of 100 microg/mL methylene blue (MB) and toluidine blue (TB) as photosensitizers. The light source was Indium-Gallium-Aluminum Phosphide (InGaAIP) laser at 53 J/cm2. Suspensions of 108 cells/mL of C. albicans were subject to PDT for 5 minutes in 96-well plates, then decimal dilutions were plated on Sabouraud Dextrose agar After 48h incubation at 37 degreesC, the number of CFU/mL were obtained and submitted to statistical analysis using Kolmogorov-Smirnov, ANOVA (p<0.0001) and Tukey tests. The results showed that MB or laser irradiation alone did not have statistically significant antifungal activity compared to the positive control group (p> 0. 05). Conversely, the number of viable C. albicans cells was reduced significantly after PDT using MB or mainly TB associated to diode laser irradiation. The data proved the efficacy of PDT against C. albicans cells, regardless of the photosensitizer used. PMID:22165318

  14. In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform.

    PubMed

    Liu, Xiaomin; Que, Ivo; Kong, Xianggui; Zhang, Youlin; Tu, Langping; Chang, Yulei; Wang, Tong Tong; Chan, Alan; Löwik, Clemens W G M; Zhang, Hong

    2015-09-28

    A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the (1)O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, (1)O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm(-2)) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy. PMID:26300064

  15. Primary Prevention of Skin Dysplasia in Renal Transplant Recipients With Photodynamic Therapy: A Randomized Controlled Trial.

    PubMed

    Togsverd-Bo, K; Omland, S H; Wulf, H C; Sørensen, S S; Haedersdal, M

    2015-11-01

    Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p?=?0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n?=?43) compared with PDT-treated skin (n?=?8), p?=?0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR. PMID:26018207

  16. Inhibition of NF-?B in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy

    PubMed Central

    Broekgaarden, Mans; Kos, Milan; Jurg, Freek A.; van Beek, Adriaan A.; van Gulik, Thomas M.; Heger, Michal

    2015-01-01

    Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor ?B (NF-?B) has been identified as a potential pharmacological target, albeit inhibition of NF-?B may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-?B in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-?B in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells. PMID:26307977

  17. Encapsulation of palladium porphyrin photosensitizer in layered metal oxide nanoparticles for photodynamic therapy against skin melanoma

    NASA Astrophysics Data System (ADS)

    Chen, Zih-An; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Chang, Yu-Chuan; Liu, Chen-Lun; Weng, Ching-Feng; Mou, Chung-Yuan; Lee, Chia-Hung

    2015-10-01

    We designed a biodegradable nanocarrier of layered double hydroxide (LDH) for photodynamic therapy (PDT) based on the intercalation of a palladium porphyrin photosensitizer (PdTCPP) in the gallery of LDH for melanoma theragnosis. Physical and chemical characterizations have demonstrated the photosensitizer was stable in the layered structures. In addition, the synthesized nanocomposites rendered extremely efficacious therapy in the B16F10 melanoma cell line by improving the solubility of the hydrophobic PdTCPP photosensitizer. The detection of singlet oxygen generation under irradiation at the excitation wavelength of a 532 nm laser was indeed impressive. Furthermore, the in vivo results using a tumour xenograft model in mice indicated the apparent absence of body weight loss and relative organ weight variation to the liver and kidney demonstrated that the nanocomposites were biosafe with a significant reduction in tumour volume for the anti-cancer efficacy of PDT. This drug delivery system using the nanoparticle-photosensitizer hybrid has great potential in melanoma theragnosis.

  18. Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature

    PubMed Central

    Kikuchi, Takeshi; Mogi, Makio; Okabe, Iichiro; Okada, Kosuke; Goto, Hisashi; Sasaki, Yasuyuki; Fujimura, Takeki; Fukuda, Mitsuo; Mitani, Akio

    2015-01-01

    Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT) has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy. PMID:26473843

  19. Water-soluble benzylidene cyclopentanone photosensitizers for two-photon excited photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fang, Yanyan; Zhao, Hongyou; Zou, Qianli; Zhao, Yuxia; Gu, Ying; Wu, Feipeng

    2013-12-01

    A series of benzylidene cyclopentanone photosensitizers modified by polyethylene glycol, carboxylate anionic or pyridyl cationic groups with gradient lipid-water partition coefficients were reported. Detailed characterization and systematic studies of these photosensitizers, including their linear and nonlinear photophysical properties, in vitro photodynamic therapy (PDT) and two-photon excited PDT (2PE-PDT) activities were conducted and compared with a clinical drug PSD-007 (a mixture of porphyrins). Three of them exhibited appropriate lipid-water partition coefficients, high reactive oxygen yields, large two-photon absorption cross-section and low dark toxicity under therapy dosage, could be absorbed efficiently by liver hepatocellular HepG2 cells and presented strong PDT and 2PE-PDT activity by in vitro cell experiments. Furthermore, in vivo tumor experiments were carried out on BALB/c mouse models using B3 as the photosensitizer. The results showed that the tumor growth could be effectively suppressed by B3 under 2PE-PDT. This work demonstrated the feasibility of using a simple molecular structure to construct high efficient photosensitizers for 2PE-PDT.

  20. Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis.

    PubMed

    Gualberto, Erivan Clementino; Theodoro, Letícia Helena; Longo, Mariellén; Novaes, Vivian Cristina Noronha; Nagata, Maria José Hitomi; Ervolino, Edilson; Garcia, Valdir Gouveia

    2016-01-01

    The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n?=?180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini-pumps containing either vehicle or nicotine were implanted in the rats 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30 days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine. PMID:26545755

  1. Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1995-03-01

    From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

  2. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  3. Role of Toll-like receptors in photodynamic-therapy-elicited host response

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    2004-07-01

    Treatment of solid tumors by photodynamic therapy (PDT) induces a host reaction, coordinated through a network of inflammatory and immune responses, that plays an important role in the therapy outcome. It is suggested that this host response is initiated by altered self-associated endogenous danger signals massively released from PDT-treated tumors. Toll-like receptors, localized predominantly in the membrane of immune cells, are the major sensors of the recognition arm of the innate immune system. The engagement of these receptors by PDT-generated danger signals prompts the activation of the networks of innate immunity signaling pathways leading to the downstream activation of nuclear transcription factors responsible for the transcription of inflammatory/immune response-associated genes. The contribution of PDT-induced host response to the therapeutic outcome depends on the balance between the tissue-destructive action of inflammatory/immune effectors and the impact of concomitantly mobilized negative regulatory mechanisms evolved for controlling the intensity and duration of inflammatory and immune responses.

  4. Photodynamic therapy for recurrent and residual malignant tumors of the oropharyngeal area

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Garbusov, Max I.; Markitchev, Nikolai A.; Riabov, Michail V.

    1999-12-01

    The frequency of tumor recurrences, according to the modern literature, remains high even in early stages of cancer (15% to 35%), the efficacy of conventional therapy for recurrent tumors is insufficient. In the State Research Center for Laser Medicine in 1992-97 photodynamic therapy with russian photosensitizers Photoheme ((lambda) equals 630 nm) and Photosense ((lambda) equals 670 nm) has been applied to 42 patients with recurrent and/or residual tumors (size corresponding to T1 - T4 symbols) of oropharyngeal area. We used laser irradiation for 3 - 30 minutes, power density used was from 0.05 to 1.0 W/cm2, energy density - 300 J/cm2. Therapeutic effect in term from 3 to 45 months was achieved in 39 (92.9%) patients. Complete resorption of tumors took place in 23 (54.8%) cases, partial resorption - in 16 (38.1%); in 3 cases (7.1%) the results of PDT were assessed as no response (tumor size decrease by less than 50%). Absolute resistance to PDT has not been noticed. The data obtained shows that PDT is a promising treatment modality for managing recurrent and residual tumors of oropharyngeal area.

  5. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma.

    PubMed

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I-II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%-0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  6. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections.

    PubMed

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-01-01

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O?, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores. PMID:26343645

  7. Heat shock protein 70 is acute phase reactant: response elicited by tumor treatment with photodynamic therapy

    PubMed Central

    Merchant, Soroush

    2010-01-01

    Oxidative stress in photodynamic therapy (PDT)-treated tumor cells is known to instigate a strong upregulation of the expression of heat shock proteins. However, the treatment of mouse Lewis lung carcinoma (LLC) cells with Photofrin™ PDT resulted in the upregulation of heat shock protein 70 (Hsp70) gene not only in these cells but also in co-incubated untreated Hepa 1-6 cells. To investigate whether this phenomenon extends in vivo, LLC tumors growing in C57BL/6 mice were treated with Photofrin™ PDT. The tumors and the livers from the mice were collected at 4, 8, or 24 h after therapy for quantitative reverse transcriptase polymerase chain reaction-based analysis of Hsp70 gene expression. Increased Hsp70 gene expression was detected in both the tumor and liver tissues and was most pronounced at 4 h after PDT. This effect was inhibited by treatment of host mice with glucocorticoid synthesis inhibitor metyrapone. Hsp70 protein levels in the livers of mice bearing PDT-treated tumors gradually decreased after therapy while serum levels increased at 4 h after therapy and then continually decreased. The exposure of in vitro PDT-treated LLC cells to Hsp70 and subsequent flow cytometry analysis revealed binding of this protein to cells that was dependent on PDT dose and more pronounced with dying than viable cells. Thus, following the induction of tumor injury by PDT, Hsp70 can be produced in the liver and spleen as acute phase reactant and released into circulation, from where it can be rapidly sequestered to damaged tumor tissue to facilitate the disposal of dying cells. PMID:20865355

  8. Fluorescence image-guided photodynamic therapy of cancer cells using a scanning fiber endoscope

    NASA Astrophysics Data System (ADS)

    Woldetensae, Mikias H.; Kirshenbaum, Mark R.; Kramer, Greg M.; Zhang, Liang; Seibel, Eric J.

    2013-03-01

    A scanning fiber endoscope (SFE) and the cancer biomarker 5-aminolevulinic acid (5-ALA) were used to fluorescently detect and destroy superficial cancerous lesions, while experimenting with different dosimetry levels for concurrent or sequential imaging and laser therapy. The 1.6-mm diameter SFE was used to fluorescently image a confluent monolayer of A549 human lung cancer cells from culture, previously administered with 5 mM solution of 5-ALA for 4 hours. Twenty hours after therapy, cell cultures were stained to distinguish between living and dead cells using a laser scanning confocal microscope. To determine relative dosimetry for photodynamic therapy (PDT), 405-nm laser illumination was varied from 1 to 5 minutes with power varying from 5 to 18 mW, chosen to compare equal amounts of energy delivered to the cell culture. The SFE produced 500-line images of fluorescence at 15 Hz using the red detection channel centered at 635 nm. The results show that PDT of A549 cancer cell monolayers using 405nm light for imaging and 5-ALAinduced PpIX therapy was possible using the same SFE system. Increased duration and power of laser illumination produced an increased area of cell death upon live/dead staining. The ultrathin and flexible SFE was able to direct PDT using wide-field fluorescence imaging of a monolayer of cultured cancer cells after uptaking 5-ALA. The correlation between light intensity and duration of PDT was measured. Increased length of exposure and decreased light intensity yields larger areas of cell death than decreased length of exposure with increased light intensity.

  9. Adjuvant Therapies and Patient and Tumor Characteristics Associated With Survival of Adult Patients With Adrenocortical Carcinoma

    PubMed Central

    Williams, Andrew R.; Sabolch, Aaron; Jolly, Shruti; Miller, Barbra S.; Hammer, Gary D.

    2014-01-01

    Context: Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcome and prognostic factors rely on fairly small studies. Here we summarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. Objective: The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. Design: Patient data were collected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrence-free survival in Cox regression models (multivariable and univariable). Results: Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. Conclusions: This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence. PMID:24302750

  10. Hyperbaric oxygen therapy augments the photodynamic action of methylene blue against bacteria in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, S. K.; Dadani, F. N.; Chien, C.; Wilson, B. C.

    2007-02-01

    Photodynamic therapy (PDT) entails the combination of photosensitizer and light to generate cytotoxic molecules that derive from molecular oxygen (O II). The presence of sufficient O II within the target tissues is critical to the efficiency of PDT. This study investigates the use of hyperbaric oxygen therapy in combination with PDT (HOTPDT) to augment the photodynamic action of methylene blue (MB) or 5-aminolevulinic acid (ALA) against gram positive and gram negative bacterial strains in vitro. Staphylococcus aureus or Pseudomonas aeruginosa were grown in trypticase soy broth as planktonic cultures (~10 8/mL) or as established biofilms in 48 well plates (3 days old) at 32°C. Dark toxicity and PDT response in the presence or absence of HOT (2 atmospheres, 100% O II for 30, 60 or 120 min) was established for both MB (0-0.1 mM) and ALA (0- 1 mM) for a range of incubation times. The number of surviving colonies (CFU/mL) was plotted for each treatment groups. Light treatments (5, 10, 20 or 30 J/cm2) were conducted using an array of halogen bulbs with a red filter providing 90% transmittance over 600-800 nm at 21 mW/cm2. HOT increased the dark toxicity of MB (30 min, 0.1 mM) from < 0.2 log cell kill to 0.5 log cell kill. Dark toxicity of ALA (4 hr, 1 mM) was negligible and did not increase with HOT. For non-dark toxic concentrations of MB or ALA, (0.05 mM and 1 mM respectively) HOT-PDT enhanced the antimicrobial effect of MB against Staphylococcus aureus in culture by >1 and >2 logs of cell kill (CFU/mL) at 5 and 10 J/cm2 light dose respectively as compared to PDT alone. HOT-PDT also increased the anti-microbial effects of MB against Staphylococcus aureus biofilms compared to PDT, albeit less so (> 2 logs) following 10 J/cm2 light dose. Anti-microbial effects of PDT using ALA were not significant for either strain with or without HOT. These data suggest that HOTPDT may be useful for improving the PDT treatment of bacterial infections.

  11. Versatile RBC-derived vesicles as nanoparticle vector of photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Leng-Yin; Shi, Xuan-Yu; Yang, Chung-Shi; Huang, Dong-Ming

    2012-12-01

    Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O2&z.rad;) and singlet oxygen (1O2) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT.Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O2&z.rad;) and singlet oxygen (1O2) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32506c

  12. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    SciTech Connect

    Chen Bin; Pogue, Brian W. . E-mail: pogue@dartmouth.edu; Hoopes, P. Jack; Hasan, Tayyaba

    2005-03-15

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm{sup 2}) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm{sup 2}) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments. Histologic studies confirmed that this combined treatment led to damage to both tumor vasculature and tumor cells. Importantly, the combined PDT treatment did not increase normal tissue damage and tissue recovered well at 60 days after treatment. Conclusions: Our results suggest that targeting both tumor vascular and cellular compartments by combining a long-interval PDT with a short-interval PDT can be an effective and safe way to enhance PDT damage to tumor tissue.

  13. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents.

    PubMed

    Patel, Seema

    2016-05-01

    Propolis is a bee-metabolized resinous substance (bee glue) from plant sap and gums. It has been in usage as a healing agent since antiquity, yet has not garnered global popularity as a health promoter. Its biological effects, which range from antimicrobial, antioxidant, anti-inflammatory, antidiabetic, dermatoprotective, anti-allergic, laxative and immunomodulatory to anticancer, have been validated. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The inhibition of matrix metalloproteinases, anti-angiogenesis, prevention of metastasis, cell-cycle arrest, induction of apoptosis and moderation of the chemotherapy-induced deleterious side effects have been deduced as the key mechanisms of cancer manipulation. The components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc. These compounds target various genetic and biochemical pathways of cancer progression. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Despite phenomenal development in cancer research, conventional therapy falls short in complete malignancy management. The findings obtained so far build hope that propolis as a complementary medicine may address the lacunae. This review documents the recent advances and scope of amendement in cancer remediation with adequate emphasis on the mechanistic aspect of propolis. PMID:25723108

  14. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

    PubMed Central

    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-01-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = ?2.6626 to ?0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels. PMID:24756915

  15. The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer

    PubMed Central

    Gori, Stefania; Inno, Alessandro; Fiorio, Elena; Foglietta, Jennifer; Ferro, Antonella; Gulisano, Marcella; Pinotti, Graziella; Gubiotti, Marta; Cavazzini, Maria Giovanna; Turazza, Monica; Duranti, Simona; De Simone, Valeria; Iezzi, Laura; Bisagni, Giancarlo; Spazzapan, Simon; Cavanna, Luigi; Saggia, Chiara; Bria, Emilio; Cretella, Elisabetta; Vici, Patrizia; Santini, Daniele; Fabi, Alessandra; Garrone, Ornella; Frassoldati, Antonio; Amaducci, Laura; Saracchini, Silvana; Evangelisti, Lucia; Barni, Sandro; Gamucci, Teresa; Mentuccia, Lucia; Laudadio, Lucio; Zoboli, Alessandra; Marchetti, Fabiana; Bogina, Giuseppe; Lunardi, Gianluigi; Boni, Luca

    2015-01-01

    Background The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients. Methods Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted. Results Among 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001). Conclusions The majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant systemic therapy or receiving adjuvant systemic therapy without trastuzumab. PMID:26340098

  16. The effect of motexafin gadolinium on ALA photodynamic therapy in glioma spheroids

    NASA Astrophysics Data System (ADS)

    Mathews, Marlon S.; Sanchez, Rogelio; Sun, Chung-Ho; Madsen, Steen J.; Hirschberg, Henry

    2008-02-01

    Following surgical removal of malignant brain tumors 80% of all cases develop tumor recurrence within 2 cm of the resected margin. The aim of postoperative therapy is therefore elimination of nests of tumor cells remaining in the margins of the resection cavity. Light attenuation in tissue makes it difficult for adequate light fluences to reach depths of 1-2 cm in the resection margin making it difficult for standard intraoperative photodynamic therapy (PDT) to accomplish this goal. Thus additional agents are required that either increase the efficacy of low fluence PDT or inhibit cellular repair, to enhance effectiveness of PDT in the tumor resection cavity. Motexafin gadolinium (MGd) is one such agent previously reported to enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents by causing redox stress to cancerous cells. MGd is well tolerated with tumor specific uptake in clinical studies. The authors evaluated MGd as a potential PDT enhancing agent at low light fluences using an in vitro model. Multicellular Glioma spheroids (MGS) of approximately 300 micron diameter, obtained from ACBT cell lines were subjected to acute PDT treatments at 6J, 12J, and 18J light fluences. Growth was determined by measuring diameters in two axes. At four weeks a dose dependent inhibition of spheroid growth was seen in 33%, 55%, and 83% of the MGS at 6J, 12J, and 18J respectively, while inhibition followed by a partial reversal of growth was seen in 17%, 33%, and 17% respectively. This study provides a rationale for the use of this drug as a PDT enhancer in the management of brain tumors.

  17. Cerebral Edema Following Photodynamic Therapy Using Endogenous and Exogenous Photosensitizers in Normal Brain

    PubMed Central

    Mathews, Marlon S.; Chighvinadze, David; Gach, H. Michael; Uzal, Francisco A.; Madsen, Steen J.; Hirschberg, Henry

    2014-01-01

    Background and Objective Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy such as photodynamic therapy (PDT) could be of benefit. The increase in brain edema following PDT using endogenous and exogenous photosensitizers was compared in terms of animal survival, MR imaging, and histopathological changes in normal brain. Materials and Methods Fischer rats were exposed to increasing laser light treatment following intraperitoneal injection of either the photosensitizers 5-aminolevulinic acid (ALA) or aluminum phthalocyanine disulfonate (AlPcS2a). Light treatment was applied either via an optical fiber inserted directly into the brain parenchyma or through a fiber applied to the surface of the intact skull. Edema development was followed by T2-weighted MR imaging. Results ALA and AlPcS2a PDT resulted in a fluence dependent increase in cerebral edema and mortality. AlPcS2a PDT showed significant edema and mortality even at low fluences following interstitial light delivery, which was reduced with surface illumination. The mechanism of edema was determined to be vasogenic by response to steroid therapy and confirmed on histological images. Conclusions T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and noninvasive modality in following the development of the edema reaction and the degree and time course of blood–brain barrier dysfunction thus allowing the use of fewer animals. ALA mediated PDT induced a lower edema reaction than that observed with the photosensitizer AlPcS2a. PMID:22006731

  18. Photodynamic therapy can induce non-specific protective immunity against a bacterial infection

    NASA Astrophysics Data System (ADS)

    Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Kinoshita, Manabu; Morimoto, Yuji; Hamblin, Michael R.

    2012-03-01

    Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X107 CFU) into the mouse knee followed 3 days later by 1 ?g of Photofrin and 635- nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection.

  19. Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

    PubMed

    Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2015-08-15

    Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as ? stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. PMID:26117192

  20. Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors.

    PubMed

    Ganz, P A; Rowland, J H; Meyerowitz, B E; Desmond, K A

    1998-01-01

    Little is known about the long-term effects of adjuvant therapy on quality of life, sexual functioning and symptoms in breast cancer survivors. Between January 1996 and June 1997, we surveyed 1098 women who had been diagnosed with early stage breast cancer between 1 and 5 years earlier. The breast cancer survivors were recruited in two large metropolitan centers in the USA. They completed a survey battery that contained standardized measures of health-related quality of life (HRQL), depression, body image, sexual functioning, and symptoms. A total of 1096 had usable responses for these analyses. In this sample, n = 356 had received tamoxifen (TAM) alone, n = 180 received chemotherapy (CHEM) alone, n = 395 received CHEM + TAM, and n = 265 received no adjuvant therapy (NO RX). There were significant differences in the mean age of each group, with the TAM group being the oldest (mean 62.6 years) and the CHEM group being the youngest (mean 46.8 years). Both age and time since diagnosis were controlled for in all statistical analyses. We found no significant differences in global quality of life among the four treatment groups. For the MOS-SF-36, there were no significant differences on the subscale scores except for the physical functioning subscale (p = 0.0002); the NO RX group had the highest functioning. There were no significant differences in depression scores among the four treatment groups. The MOS-SF-36 physical functioning composite score differed by treatment group (p = 0.012); the NO RX group had a physical functioning composite score that was at the mean for a normal healthy population of women, while those in the adjuvant treatment groups scored slightly lower. The mental health composite score was not significantly different among the four treatment groups and approximated scores from the normal population of healthy women. There were no differences in body image scores among the four treatment groups; however, sexual functioning scores did differ (p = 0.0078) with patients receiving chemotherapy (either alone or with tamoxifen) experiencing more problems. Hot flashes, night sweats, and vaginal discharge differed by treatment (p = 0.0001); all symptoms were reported more often in breast cancer survivors on tamoxifen. Vaginal dryness and pain with intercourse also differed significantly by adjuvant treatment, occurring more often in survivors treated with chemotherapy. Overall, breast cancer survivors function at a high level, similar to healthy women without cancer. However, compared to survivors with no adjuvant therapy, those who received chemotherapy have significantly more sexual problems, and those treated with tamoxifen experience more vasomotor symptoms. PMID:9928575

  1. Pulsed light imaging for wide-field dosimetry of photodynamic therapy in the skin

    NASA Astrophysics Data System (ADS)

    Davis, Scott C.; Sexton, Kristian; Chapman, Michael Shane; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Photodynamic therapy using aminoluvelinic acid (ALA) is an FDA-approved treatment for actinic keratoses, pre-cancerous skin lesions which pose a significant risk for immunocompromised individuals, such as organ transplant recipients. While PDT is generally effective, response rates vary, largely due to variations in the accumulation of the photosensitizer protoporphyrin IX (PpIX) after ALA application. The ability to quantify PpIX production before treatment could facilitate the use of additional interventions to improve outcomes. While many groups have demonstrated the ability to image PpIX in the clinic, these systems generally require darkening the room lights during imaging, which is unpopular with clinicians. We have developed a novel wide-field imaging system based on pulsed excitation and gated acquisition to image photosensitizer activity in the skin. The tissue is illuminated using four pulsed LED's to excite PpIX, and the remitted light acquired with a synchronized ICCD. This approach facilitates real-time background subtraction of ambient light, precluding the need to darken the exam room. Delivering light in short bursts also allows the use of elevated excitation intensity while remaining under the maximum permissible exposure limits, making the modality more sensitive to photosensitizer fluorescence than standard approaches. Images of tissue phantoms indicate system sensitivity down to 250nM PpIX and images of animals demonstrate detection of PpIX fluorescence in vivo under normal room light conditions.

  2. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis.

    PubMed

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-01-01

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58-80 years), and the stages of cancer were IIA-IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%-100%), 15% (range, 15%-99%), and 15% (range 15%-60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction. PMID:26512656

  3. Iron chelators in photodynamic therapy revisited: synergistic effect by novel highly active thiosemicarbazones.

    PubMed

    Mrozek-Wilczkiewicz, Anna; Serda, Maciej; Musiol, Robert; Malecki, Grzegorz; Szurko, Agnieszka; Muchowicz, Angelika; Golab, Jakub; Ratuszna, Alicja; Polanski, Jaroslaw

    2014-04-10

    In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe(2+) forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe(2+) affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX. PMID:24900837

  4. Photodynamic therapy-induced programmed cell death in carcinoma cell lines

    NASA Astrophysics Data System (ADS)

    He, Xiao-Yan; Sikes, Robert A.; Thomsen, Sharon L.; Chung, L.; Jacques, Steven L.

    1993-06-01

    The mode of cell death following photodynamic therapy (PDT) was investigated from the perspective of programmed cell death (apoptosis). Human prostate carcinoma cells (PC3), human non-small cell lung carcinoma (H322a), and rat mammary carcinoma (MTF7) were treated by PDT following sensitization with dihematoporphyrin ether (DHE). The response of these carcinoma cell lines to PDT was variable. An examination of extracted cellular DNA by gel electrophoresis showed the characteristic DNA ladder pattern indicative of internucleosomal cleavage of DNA during apoptosis. MTF7 and PC3 responded to PDT by inducing apoptosis while H322a had no apoptotic response. The magnitude of the response and the PDT dosage required to induce the effect were different in PC3 and MTF7. MTF7 cells responded with rapid apoptosis at the dose of light and drug that yielded 50% cell death (LD50). In contrast, PC3 showed only marginal apoptosis at the LD50 but had a marked response at the LD85. Furthermore, the onset of apoptosis followed slower kinetics in PC3 (2 hr - 4 hr) than in MTF7 (< 1 hr). H322a cells were killed by PDT but failed to exhibit any apoptotic response. This study indicates that apoptosis may occur during PDT induced cell death, but this pathway is not universal for all cancer cell lines.

  5. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    SciTech Connect

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  6. Protoporphyrin IX-Gold Nanoparticle Conjugates for Targeted Photodynamic Therapy--An In-Vitro Study.

    PubMed

    Savarimuthu, Wilfred Prasanna; Gananathan, Poorani; Rao, Aruna Prakasa; Manickam, Elanchezhiyan; Singaravelu, Ganesan

    2015-08-01

    Targeted drug delivery system using nanoparticles is a promising strategy for efficient Photodynamic therapy (PDT) as they have the potential to overcome the problems of photosensitizer and enhance the effectiveness and specificity of PDT. In this study, Protoporphyrin IX (PpIX) conjugated gold nanoparticles were synthesized using electrostatic and covalent conjugation scheme. Folic acid (FA) was also conjugated suitably to the covalent complex to vectorize the complex. Optical characterizations of the complex prove the formation of the complex. The size of the synthesized nanocomplexes was studied using light scattering measurements. The photo-toxicity of the free PpIX and PpIX-nanoparticle complexes were studied using MTT assay technique against Vero and HeLa cell lines. These In-vitro results of this study indicates that, the nanoparticle complexes are more phototoxic compared to free PpIX, with the covalent complex being the better of the two complexes and the folate-mediated nanocomplex is the superior of the studied complexes. These results ensures that nanoparticle conjugated photosensitizers equipped with FA may be an effective drug delivery mechanism for PDT. PMID:26369120

  7. Light based anti-infectives: ultraviolet C irradiation, photodynamic therapy, blue light, and beyond

    PubMed Central

    Yin, Rui; Dai, Tianhong; Avci, Pinar; Jorge, Ana Elisa Serafim; de Melo, Wanessa CMA; Vecchio, Daniela; Huang, Ying-Ying; Gupta, Asheesh; Hamblin, Michael R

    2013-01-01

    Owing to the worldwide increase in antibiotic resistance, researchers are investigating alternative anti-infective strategies to which it is supposed microorganisms will be unable to develop resistance. Prominent among these strategies, is a group of approaches which rely on light to deliver the killing blow. As is well known, ultraviolet light, particularly UVC (200–280nm), is germicidal, but it has not been much developed as an anti-infective approach until recently, when it was realized that the possible adverse effects to host tissue were relatively minor compared to its high activity in killing pathogens. Photodynamic therapy is the combination of non-toxic photosensitizing dyes with harmless visible light that together produce abundant destructive reactive oxygen species (ROS). Certain cationic dyes or photosensitizers have good specificity for binding to microbial cells while sparing host mammalian cells and can be used for treating many localized infections, both superficial and even deep-seated by using fiber optic delivered light. Many microbial cells are highly sensitive to killing by blue light (400–470 nm) due to accumulation of naturally occurring photosensitizers such as porphyrins and flavins. Near infrared light has also been shown to have antimicrobial effects against certain species. Clinical applications of these technologies include skin, dental, wound, stomach, nasal, toenail and other infections which are amenable to effective light delivery. PMID:24060701

  8. Preliminary study of transurethral photodynamic therapy mediated with Tookad in a canine prostate model

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Hetzel, Fred W.; Chen, Qun; Dole, Kenneth C.

    2008-02-01

    Background: photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad (pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer. Our previous studies show that Tookad PDT can induce marked prostatic tissue lesion but minimal urethral lesion. In this study a transurethral procedure was used to evaluate the response of the prostatic urethra to direct urethral irradiation. Materials and Methods: Tookad solution (2.5 mg/ml) was administered (1 mg/kg) through IV catheter by an infusion pump over 10 min. A diffuser fiber (1 cm active length) was inserted into the prostatic urethra. The light irradiation (50 or 100 J/cm) started at 4 min after the onset of drug infusion. Urinalysis was performed for 24 - 48 h post PDT. One week after PDT, prostates (n = 4) were removed at necropsy and subjected to histopathological examination. Results: The cross section of prostates showed severe hemorrhagic and necrotic lesions on the right lobe. The diameter of the lesion, measured from urethra to capsule, was >13 mm for 50 J/cm treatment and >18 mm for 100 J/cm, respectively. Although underlying periurethral lesion was visible, the urethral surface was intact and prostatic urethra was open. Conclusions: The joint point of the diffuser tip and the guide fiber might be bent while passing through the sharp turn at the Ischial Arch, which could affect the light distribution and cause the asymmetric lesion. Nonetheless, the transurethral direct irradiation can induce marked prostatic tissue lesion but minimal urethral lesion.

  9. Development and comparison of two devices for treatment of onychomycosis by photodynamic therapy.

    PubMed

    da Silva, Ana Paula; Chiandrone, Daniel José; Tinta, Jefferson Wanderson Rossi; Kurachi, Cristina; Inada, Natalia Mayumi; Bagnato, Vanderlei Salvador

    2015-06-01

    Onychomycosis is the most common nail disorder. The treatment for this type of infection is one of the main difficult ones in clinical practice, due to the fact that the nails are nonvascularized structures, which compromise the penetration of drugs delivered systemically and favor slow nail growth. We present two devices based on light-emitting diode arrays as light sources for the treatment of onychomycosis by photodynamic therapy (PDT). PDT is an emerging technique that uses a photosensitizer (PS) activated by light in the presence of oxygen. The PS absorbs energy from light and transfers it to oxygen, producing reactive oxygen species such as hydroxyl radicals, superoxide, and singlet oxygen which inactivate fungi and bacteria. Our proposal is the use of a portable and secure light source device in patients with onychomycosis. Additional advantages are the low cost involved, the possibility of topical treatment rather than systemic and the simplicity of operation. These advantages are important to ensure the implementation of this technology for the treatment of an impacting health problem. PMID:25954977

  10. The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit

    PubMed Central

    Lee, Young-Ho; Park, Ho-Won; Lee, Ju-Hyun; Seo, Hyun-Woo; Lee, Si-Young

    2012-01-01

    The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain–heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose. PMID:23222991

  11. Interstitial photodynamic therapy and glioblastoma: light fractionation study on a preclinical model: preliminary results

    NASA Astrophysics Data System (ADS)

    Leroy, Henri-Arthur; Vermandel, Maximilien; Tétard, Marie-Charlotte; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas

    2015-03-01

    Background Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a local treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen to form cytotoxic species. Fractionation of light delivery may enhance treatment efficiency by restoring tissue oxygenation. Objectives To evaluate the efficiency of light fractionation using MRI imaging, including diffusion and perfusion, compared to histological data. Materials and Methods Thirty-nine "Nude" rats were grafted with human U87 cells into the right putamen. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomized in three groups: without illumination, with monofractionated illumination and the third one with multifractionated light. Treatment effects were assessed with early MRI including diffusion and perfusion sequences. The animals were eventually sacrificed to perform brain histology. Results On MRI, we observed elevated diffusion values in the center of the tumor among treated animals, especially in multifractionated group. Perfusion decreased around the treatment site, all the more in the multifractionated group. Histology confirmed our MRI findings, with a more extensive necrosis and associated with a rarified angiogenic network in the treatment area, after multifractionated PDT. However, we observed more surrounding edema and neovascularization in the peripheral ring after multifractionated PDT. Conclusion Fractionated interstitial PDT induced specific tumoral lesions. The multifractionated scheme was more efficient, inducing increased tumoral necrosis, but it also caused significant peripheral edema and neovascularization. Diffusion and perfusion MRI imaging were able to predict the histological lesions.

  12. Effects of vascular photodynamic therapy in a newly adapted experimental rat aortic aneurysm model†

    PubMed Central

    Heckenkamp, Joerg; Luebke, Thomas; Theis, Thorsten; Schumacher, Lukas; Gawenda, Michael; Thul, Roland; Fries, Jochen W.U.; Brunkwall, Jan

    2012-01-01

    The hypothesis driving this study was that photodynamic therapy (PDT) may limit abdominal aortic aneurysm growth due to matrix changes. The aortas of 12 rats were incubated with elastase using a newly modified experimental aneurysm model (3.5 mg/ml). Rats were allocated to an elastase-only group (n = 6) to study the elastase-induced aneurysm growth and an elastase ± PDT group to evaluate if PDT limited aneurysm growth (n = 6). PDT was performed with the photosensitizer methylene blue, and thermoneutral laser light (660 nm) was applied (120 J/cm2, 100 mW/cm2) using a diode laser. Four untreated rats served as controls. The arteries were analysed after 4 weeks based on histology, immunohistochemistry and morphometry. This modified rat elastase model led to reproducible aneurysm development with no elastase-induced mortality compared with control animals (circumference, controls: 2.9 ± 0.2 vs. elastase: 5.5 ± 0.9 mm; P < 0.01). PDT after elastase incubation did not inhibit inflammatory cell infiltration. No significant change in the circumference was observed between elastase incubation and PDT treatment after elastase incubation (circumference, elastase: 5.5 ± 0.9 vs. elastase and PDT: 6.1 ± 0.8 mm; P < 0.01). Despite a PDT-induced resistance to protease digestion, PDT did not reduce aortic dilatation in the elastase-treated rat aorta. These findings suggest that PDT may not be a useful modality to prevent aneurysm growth. PMID:22493098

  13. Design of a protocol for combined laser hyperthermia-photodynamic therapy in the esophagus

    SciTech Connect

    London, R A; Eichler, J; Liebetrudt, J; Ziegenhagen, L

    2000-02-01

    Photodynamic laser therapy (PDT) for esophageal cancer has recently been studied in animal and clinical trials. In several animal experiments a synergetic effect was found by simultaneously applying PDT and hyperthermia (HT). In this paper an optical fiber system is described which can be used in the esophagus for combined PDT with a 1 W dye laser and HT with a 15--40 W Nd-YAG laser. Phantoms were developed to simulate the geometry of the esophagus using cow muscle. The spatial-temporal temperature field during HT was measured. The results were compared with calculations using a coupled Monte Carlo laser transport/finite difference heat transport model using the LATIS computer program. Measurements and calculations yield a realistic description of the temperature distribution during HT under various experimental conditions. The LATIS program allows the prediction of the effects of blood perfusion for in-vivo situations. The results show that the perfusion has considerable influence on the temperature field, which must be considered for in-vivo applications.

  14. Titania coated upconversion nanoparticles for near-infrared light triggered photodynamic therapy.

    PubMed

    Lucky, Sasidharan Swarnalatha; Muhammad Idris, Niagara; Li, Zhengquan; Huang, Kai; Soo, Khee Chee; Zhang, Yong

    2015-01-27

    Because of the limited penetration depth of visible light that generally excites most of the available photosensitizers (PSs), conventional photodynamic therapy (PDT) is limited to the treatment of superficial and flat lesions. Recently, the application of deep penetrating near-infrared (NIR) light excitable upconversion nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in the treatment of solid tumors due to its ability to penetrate thick tissue. However, various constructs developed so far have certain limitations such as poor or unstable PS loading, reducing their therapeutic efficacy and limiting their application to solution or cell-based studies. In this work, we present a method to fabricate uniform core-shell structured nanoconstruct with a thin layer of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN core. Our design allows controllable and highly reproducible PS loading, preventing any leakage of PS compared to previously developed nanoconstructs, thus ensuring repeatable PDT results. Further surface modification of the developed nanoconstructs with polyethylene glycol (PEG) rendered them biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo. PMID:25564723

  15. Mechanisms in photodynamic therapy: photosensitizers and cellular localization on K562 cells

    NASA Astrophysics Data System (ADS)

    Ion, Rodica-Mariana; Neagu, Monica; Manda, Gina; Constantin, Carolina; Calin, Mihaela

    2007-07-01

    This paper proposes to explore the pattern of lymphoblastic cell line K562 cells death, the effects on their cell cycle induced by 5,10,15,20-tetra-p-sulphonato-phenyl-porphyrin-based photodynamic therapy (TS 4PP-PDT). Flow cytometry combined with Annexin V-FITC/PI labeling was used to detect the pattern of K562 cells' death induced by TS 4PP-PDT. These effects frequently lead to induction of apoptosis by the mitochondrial pathway involving caspases. The transmission electron microscope (TEM) and confocal laser scanning microscopy (CLSM) were used to detect the localization and time-biodistribution of sensitizers in the cells. After 1 h of TS 4PP administration, the sensitizer shows a non-uniform distribution, following that after 4h of administration, the sensitizer to be localized in some cellular targets and an increased fluorescence intensity is being detected. After 8 h and 24 h post-administration, the sensitizer is released from the cells and the light-irradiation (He-Ne laser, ?=632.8 nm) could start. Immediately after irradiation, many typical apoptotic bodies were seen in the cells treated. Most of the cells treated were necrotic at 24 hours following irradiation.

  16. Antimicrobial photodynamic therapy for inactivation of biofilms formed by oral key pathogens

    PubMed Central

    Cieplik, Fabian; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

    2014-01-01

    With increasing numbers of antibiotic-resistant pathogens all over the world there is a pressing need for strategies that are capable of inactivating biofilm-state pathogens with less potential of developing resistances in pathogens. Antimicrobial strategies of that kind are especially needed in dentistry in order to avoid the usage of antibiotics for treatment of periodontal, endodontic or mucosal topical infections caused by bacterial or yeast biofilms. One possible option could be the antimicrobial photodynamic therapy (aPDT), whereby the lethal effect of aPDT is based on the principle that visible light activates a photosensitizer (PS), leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induce phototoxicity immediately during illumination. Many compounds have been described as potential PS for aPDT against bacterial and yeast biofilms so far, but conflicting results have been reported. Therefore, the aim of the present review is to outline the actual state of the art regarding the potential of aPDT for inactivation of biofilms formed in vitro with a main focus on those formed by oral key pathogens and structured regarding the distinct types of PS. PMID:25161649

  17. The apoptosis induced by HMME-based photodynamic therapy in rabbit vascular smooth muscle cells

    NASA Astrophysics Data System (ADS)

    Yin, Huijuan; Li, Xiaoyuan; Lin, Hong; Liu, Jianzhong; Yu, Hongkui

    2007-02-01

    Objective To study the effects of HMME-based photodynamic therapy on proliferation and apoptosis of rabbit vascular smooth muscle cells(VSMCs). Method The cytotoxic effect of HMME-PDT on rabbit vascular smooth muscle cells was studied by means of Trypan Blue assay, HMME at 10?g/ml concentration and the light dose at 2.4~4.8 J/cm2 were selected in the studies. The morphological character 24h post-PDT was investigated by HE Staining. Annexin V and propidium iodide (PI) binding assays were performed to analyze the characteristics of cell death after HMME-PDT. Furthermore, The intracellular distributions of the HMME were measured by the confocal laser scanning microscope. Result It was showed the photocytotoxity to VSMC cells was dose related by Trypan Blue assay. Histology observing suggests HMME-PDT could induce cell death through apoptosis or necrosis, and the apoptosic rate was up to 50.5% by AnnexinV /PI assay. Moreover, the fluorescence images of HMME intracellular localization demonstrated that the HMME diffused into the mitochondria. Conclusion HMME-PDT could significantly inhibite VSMC proliferation and induce apoptosis.

  18. Adjunctive arterial injury and photodynamic therapy with aluminium disulphonated phthalocyanine inhibits intimal hyperplasia

    NASA Astrophysics Data System (ADS)

    Nyamekye, Isaac; McEwan, Jean R.; MacRobert, Alexander J.; Bishop, Christopher C. R.; Bown, Stephen G.

    1994-12-01

    Photodynamic therapy (PDT) of proliferative vascular smooth muscle cells (SMC) reduces intimal hyperplasia (FCIH). We assess the effects of adjunctive balloon injury and immediate PDT on contractile SMC, using aluminum disulphonated phthalocyanine (AlS2Pc) sensitization, on intimal hyperplasia. Groups of 5 Wistar rats underwent tail vein injection with 2.5 mg/kg of aluminum disulphonated phthalocyanine (AlS2Pc). Standard carotid artery balloon injury was performed with a 2FG Fogarty embolectomy catheter and the artery irradiated with 50 J/cm2. Control groups were also studied. Rats were killed at 2 and 4 weeks after treatment and perfusion fixed H&E stained cross-sections assessed by computerized morphometric measurements. Three sections per rat were analyzed. PDT treated arteries were free of FCIH formation in all cases. Laser alone (and to a lesser extent sensitizer alone) produced some reduction in the levels of FCIH compared to untreated but balloon injured vessels. The ratio of the area of intimal hyperplasia in treated vessels to the area of intimal hyperplasia in untreated (balloon only) rats were sensitizer only 98%, laser only 68% and PDT 0% at 4 weeks. PDT given at the time of angioplasty may be affective in the management of restenosis.

  19. The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit.

    PubMed

    Lee, Young-Ho; Park, Ho-Won; Lee, Ju-Hyun; Seo, Hyun-Woo; Lee, Si-Young

    2012-12-01

    The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain-heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose. PMID:23222991

  20. Multifunctional Peptide-Conjugated Hybrid Silica Nanoparticles for Photodynamic Therapy and MRI

    PubMed Central

    Benachour, Hamanou; Sève, Aymeric; Bastogne, Thierry; Frochot, Céline; Vanderesse, Régis; Jasniewski, Jordane; Miladi, Imen; Billotey, Claire; Tillement, Olivier; Lux, François; Barberi-Heyob, Muriel

    2012-01-01

    Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles. PMID:23082101

  1. Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

    PubMed Central

    Rocha, Luis B.; Schaberle, Fábio; D?browski, Janusz M.; Simões, Sérgio; Arnaut, Luis G.

    2015-01-01

    We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. PMID:26670231

  2. Antimicrobial strategies centered around reactive oxygen species--bactericidal antibiotics, photodynamic therapy, and beyond.

    PubMed

    Vatansever, Fatma; de Melo, Wanessa C M A; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-11-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics and nonpharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma, and medicinal honey. A brief final section covers reactive nitrogen species and related therapeutics, such as acidified nitrite and nitric oxide-releasing nanoparticles. PMID:23802986

  3. Multi-function microsystem for cells migration analysis and evaluation of photodynamic therapy procedure in coculture

    PubMed Central

    Jastrzebska (Jedrych), Elzbieta; Grabowska-Jadach, Ilona; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew

    2012-01-01

    Cell migration is an important physiological process, which is involved in cancer metastasis. Therefore, the investigation of cell migration may lead to the development of novel therapeutic approaches. In this study, we have successfully developed a microsystem for culture of two cell types (non-malignant and carcinoma) and for analysis of cell migration dependence on distance between them. Finally, we studied quantitatively the influence of photodynamic therapy (PDT) procedures on the viability of pairs of non-malignant (MRC5 or Balb/3T3) and carcinoma (A549) cells coculture. The proposed geometry of the microsystem allowed for separate introduction of two cell lines and analysis of cells migration dependence on distance between the cells. We found that a length of connecting microchannel has an influence on cell migration and viability of non-malignant cells after PDT procedure. Summarizing, the developed microsystem can constitute a new tool for carrying out experiments, which offers a few functions: cell migration analysis, carcinoma and non-malignant cells coculture, and evaluation of PDT procedure in the various steps of cell migration. PMID:24339849

  4. Antibacterial photodynamic therapy with 808-nm laser and indocyanine green on abrasion wound models

    NASA Astrophysics Data System (ADS)

    Topaloglu, Nermin; Güney, Melike; Yuksel, Sahru; Gülsoy, Murat

    2015-02-01

    Infections with pathogens could cause serious health problems, such as septicemia and subsequent death. Some of these deaths are caused by nosocomial, chronic, or burn-related wound infections. Photodynamic therapy (PDT) can be useful for the treatment of these infections. Our aim was to investigate the antibacterial effect of indocyanine green (ICG) and 808-nm laser on a rat abrasion wound model infected with the multidrug resistant Staphylococcus aureus strain. Abrasion wounds were infected with a multidrug resistant clinical isolate of S. aureus. ICG concentrations of 500, 1000, and 2000 ?g/ml were applied with a 450 J/cm2 energy dose. Temperature change was monitored by a thermocouple system. The remaining bacterial burden was determined by the serial dilution method after each application. Wounds were observed for 11 days posttreatment. The recovery process was assessed macroscopically. Tissue samples were also examined histologically by hematoxylin-eosin staining. Around a 90% reduction in bacterial burden was observed after PDT applications. In positive control groups (ICG-only and laser-only groups), there was no significant reduction. The applied energy dose did not cause any thermal damage to the target tissue or host environment. Results showed that ICG together with a 808-nm laser might be a promising antibacterial method to eliminate infections in animals and accelerate the wound-healing process.

  5. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis

    PubMed Central

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-01-01

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58–80 years), and the stages of cancer were IIA–IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%–100%), 15% (range, 15%–99%), and 15% (range 15%–60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction. PMID:26512656

  6. Photodynamic therapy induces epidermal thickening in hairless mice skin: an optical coherence tomography assessment

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Campos, Carolina P.; Freitas, Anderson Z.; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) promotes skin improvement according to many practitioners, however the immediately in vivo assessment of its response remains clinically inaccessible. As a non-invasive modality, optical coherence tomography (OCT) has been shown a feasible optical diagnostic technique that provides images in real time, avoiding tissue biopsies. For this reason, our investigation focused on evaluates the PDT effect on a rodent model by means of OCT. Therefore, a normal hairless mouse skin has undergone a single-session PDT, which was performed with topical 5- aminolevulinic acid (ALA) cream using a red (630 nm) light emitting diode (LED) which reached the light dose of 75 J/cm2. As the optical imaging tool, an OCT (930 nm) with axial resolution of 6.0 microns in air was used, generating images with contact to the mouse skin before, immediately after, 24 hours, and 2 weeks after the correspondent procedure. Our result demonstrates that, within 24 hours after ALA-PDT, the mouse skin from the PDT group has shown epidermal thickness (ET), which has substantially increased after 2 weeks from the treatment day. Moreover, the skin surface has become evener after ALA-PDT. Concluding, this investigation demonstrates that the OCT is a feasible and reliable technique that allows real-time cross-sectional imaging of skin, which can quantify an outcome and predict whether the PDT reaches its goal.

  7. Methylene blue photodynamic therapy in rats' wound healing: 21 days follow-up

    NASA Astrophysics Data System (ADS)

    Carneiro, Vanda Sanderana Macêdo; Catao, Maria Helena Chaves de Vasconcelos; Menezes, Rebeca Ferraz; Araújo, Natália Costa; Gerbi, Marleny Elizabeth Martinez

    2015-06-01

    The experimental evaluated the photodynamic therapy (PDT) in wound healing. It used 60 male rats, making two circular wounds at each animal. They were treated at 48hs intervals, with methylene blue (MB), low level laser treatment (LLLT) or both, thus resulting in PDT. The wounds were observed 01, 03, 07, 14 and 21 days after and then processed and subjected to HE staining to analyze granulation tissue, necrosis, epithelialization and collagen. After day 1, wounds treated with MB showed necrosis less intense than other groups, and the PDT group showed more intense granulation tissue. At day 3, reepithelialization was absent for half of injuries in the PDT group, and this group was also with lower collagen. However, at day 7, this same group presented reepithelialization more advanced than control group, which did not happen with those treated with MB or LLLT (p = 0.015). The results allow us to conclude that PDT difficulted reepithelization at 7th day and interfered in standard healing. However, when used separately, MB and LLLT interfered significantly compared to the control group, which did not happened to the PDT group. There was no significant difference between the treatment groups in other analysed times.

  8. Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer

    PubMed Central

    Lucena, Silvia Rocío; Salazar, Nerea; Gracia-Cazaña, Tamara; Zamarrón, Alicia; González, Salvador; Juarranz, Ángeles; Gilaberte, Yolanda

    2015-01-01

    Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer. PMID:26516853

  9. Targeting cytochrome C oxidase in mitochondria with Pt(II)-porphyrins for Photodynamic Therapy

    E-print Network

    Boersch, Michael

    2010-01-01

    Mitochondria are the power house of living cells, where the synthesis of the chemical "energy currency" adenosine triphosphate (ATP) occurs. Oxidative phosphorylation by a series of membrane protein complexes I to IV, that is, the electron transport chain, is the source of the electrochemical potential difference or proton motive force (PMF) of protons across the inner mitochondrial membrane. The PMF is required for ATP production by complex V of the electron transport chain, i.e. by FoF1-ATP synthase. Destroying cytochrome C oxidase (COX; complex IV) in Photodynamic Therapy (PDT) is achieved by the cationic photosensitizer Pt(II)-TMPyP. Electron microscopy revealed the disruption of the mitochondrial christae as a primary step of PDT. Time resolved phosphorescence measurements identified COX as the binding site for Pt(II)-TMPyP in living HeLa cells. As this photosensitizer competed with cytochrome C in binding to COX, destruction of COX might not only disturb ATP synthesis but could expedite the release of c...

  10. Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Gu, Ying; Zuo, Zhaohui; Huang, Naiyan

    2011-09-01

    Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW/cm2, 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.

  11. Transcutaneous photodynamic therapy delays the onset of paralysis in a murine multiple sclerosis model

    NASA Astrophysics Data System (ADS)

    Hunt, David W. C.; Leong, Simon; Levy, Julia G.; Chan, Agnes H.

    1995-03-01

    Photodynamic therapy (PDT) using benzoporphyrin derivative (BPD, Verteporfin) and whole body irradiation, can affect the course of adoptively transferred experimental allergic (autoimmune) encephalomyelitis (EAE) in PL mice. Murine EAE is a T cell-mediated autoimmune disease which serves as a model for human multiple sclerosis. Using a novel disease induction protocol, we found that mice characteristically developed EAE within 3 weeks of receipt of myelin basic protein (MBP)-sensitized, in vitro-cultured spleen or lymph node cells. However, if animals were treated with PDT (1 mg BPD/kg bodyweight and exposed to whole body 15 Joules cm2 of LED light) 24 hours after receiving these cells, disease onset time was significantly delayed. PDT-treated mice developed disease symptoms 45 +/- 3 days following cell administration whereas untreated controls were affected within 23 +/- 2 days. In contrast, application of PDT 48 or 120 hours following injection of the pathogenic cells had no significant effect upon the development of EAE. Experiments are in progress to account for the protective effect of PDT in this animal model. These studies should provide evidence on the feasibility of PDT as a treatment for human autoimmune disease.

  12. Photodynamic therapy affects the expression of IL-6 and IL-10 in vivo

    NASA Astrophysics Data System (ADS)

    Gollnick, Sandra O.; Musser, David A.; Henderson, Barbara W.

    1998-05-01

    Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

  13. Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

    PubMed Central

    Huggett, M T; Jermyn, M; Gillams, A; Illing, R; Mosse, S; Novelli, M; Kent, E; Bown, S G; Hasan, T; Pogue, B W; Pereira, S P

    2014-01-01

    Background: Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin. Methods: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4?mg?kg?1 verteporfin. After 60–90?min, laser light (690?nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5?J, doubling after each three patients) until 12?mm of necrosis was achieved consistently. Results: In all, 12?mm lesions were seen consistently at 40?J, but with considerable variation in necrosis volume (mean volume 3.5?cm3 at 40?J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy. Conclusions: Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds. PMID:24569464

  14. Selective treatment of atherosclerosis using photodynamic therapy in the Yucatan miniswine: preliminary results

    NASA Astrophysics Data System (ADS)

    Hsiang, York N.; Crespo, M. T.; Houston, G. T. M.; To, Eleanor C.; Todd, Mary E.; Sobeh, Mohammed S.; Greenwald, Stephen E.; Bower, Robert D.

    1994-07-01

    Photodynamic therapy (PDT) represents a novel method of selectively treating atherosclerosis using a combination of photosensitizer drug, low power laser light, and molecular oxygen. In this preliminary study, PDT was used to treat atherosclerotic lesions in a miniswine model. Yucatan miniswine weighing between 20-30 kg, were rendered atherosclerotic by a combination of balloon endothelial injury and dietary supplementation with 2% cholesterol and 15% lard diet for 7 weeks. Following this, miniswine were given a porphyrin-type photosensitizer, Photofrin 2.5 mg/kg IV. Twenty-four hours after receiving Photofrin, swine received a general anesthetic and the infrarenal abdominal aorta was exposed. Through a longitudinal aortotomy, the posterior aortic wall was irradiated with 630 nm laser light at one of the following light doses: 60, 120, and 240 J/cm2. Four weeks after PDT, swine were killed and perfusion- fixed with glutaraldehyde. Light microscopy showed a decrease in intimal thickness for all light doses. Decreased cellular elements were seen in the irradiated zones as the laser power was increased. Non-irradiated sites showed typical atherosclerotic lesions with foam cells, fibrosis and calcification. This study demonstrated the feasibility of using PDT for atherosclerotic lesions.

  15. How to monitor NF-kappaB activation after photodynamic therapy.

    PubMed

    Coupienne, Isabelle; Piette, Jacques; Bontems, Sébastien

    2010-01-01

    The nuclear factor-kappa B (NF-kappaB) is a multipotent factor involved in many cellular processes such as inflammation, immune response and embryonic development and it can be activated by a large number of stimuli. Consequently, this transcription factor plays a pivotal role in many natural processes but also in different pathologies. For several years, photodynamic therapy (PDT) has emerged as an attractive alternative approach for the treatment of different affections involving various forms of cancer and an increasing number of reports have highlighted the activation of the NF-kappaB following PDT treatment. Furthermore, it has been shown that the mechanism of activation of the NF-kappaB as well as its target genes depends on the nature of the photosensitizers and the cell type used. As this transcription factor is known to be a key regulator of the immune response but also controls cell survival and proliferation, it is important to assess its activation status and its impact on the target genes. In this review, we will present different techniques allowing identification of the activation status of this factor, from the degradation of its inhibitor in the cytoplasm to its ability to induce the expression of a reporter gene under the control of a target promoter. As a working model we will present results obtained from a 5-aminolevulinic acid-PDT treatment on cervix adenocarcinoma cells. PMID:20552341

  16. Photodynamic therapy of nonmelanoma skin malignancies with topical delta-amino levulinic acid: diagnostic measurements

    NASA Astrophysics Data System (ADS)

    Wang-Nordman, Ingrid; Svanberg, Katarina; Andersson-Engels, Stefan; Berg, Roger; Svanberg, Sune

    1995-03-01

    Photodynamic therapy (PDT) using topical application of the Protoporphyrin IX (PpIX) precursor (delta) -amino levulinic acid (ALA) in various malignant skin tumors is a new promising treatment modality. We have treated an extensive number of non-melanoma malignancies of the skin over the past three years with very satisfying initial results. For superficial, shallow lesions one treatment session is sufficient. In thicker lesions, such as nodular basal cell carcinomas, complete treatment response is achieved after two or three treatment sessions. In conjunction with the treatment procedure the tissue fluorescence and the superficial blood flow have been investigated during and after the treatment procedures. The PpIX build-up has been detected in vivo and the degree of tumor selectivity has been evaluated using laser-induced fluorescence. Also changes in the bloodflow in tumors compared to normal skin before, during, and after the treatment procedure has been followed using a laser- Doppler perfusion imaging system. Results from the measurements in basal cell carcinomas (BCCs), Mb. Bowen lesions (squamous cell carcinoma in situ) and cutaneous T-cell lymphoma lesions are presented.

  17. Stromal interactions as regulators of tumor growth and therapeutic response: A potential target for photodynamic therapy?

    PubMed Central

    Celli, Jonathan P.

    2013-01-01

    It has become increasingly widely recognized that the stroma plays several vital roles in tumor growth and development and that tumor-stroma interactions can in many cases account poor therapeutic response. Inspired by an emerging body of literature, we consider the potential role of photodynamic therapy (PDT) for targeting interactions with stromal fibroblasts and mechano-sensitive signaling with the extracellular matrix as a means to drive tumors toward a more therapeutically responsive state and synergize with other treatments. This concept is particularly relevant for cancer of the pancreas, which is characterized by tumors with a profoundly dense, rigid fibrous stroma. Here we introduce new in vitro systems to model interactions between pancreatic tumors and their mechanical microenvironment and restore signaling with stromal fibroblasts. Using one such model as a test bed it is shown here that PDT treatment is able to destroy fibroblasts in an in vitro 3D pancreatic tumor-fibroblast co-culture. These results and the literature suggest the further development of PDT as a potential modality for stromal depletion. PMID:23457416

  18. Activatable Ferritin Nanocomplex for Real-Time Monitoring of Caspase-3 Activation during Photodynamic Therapy.

    PubMed

    Wang, Jingjing; Zhang, Liwen; Chen, Minglong; Gao, Shi; Zhu, Lei

    2015-10-21

    One mechanism of photodynamic therapy (PDT) for the ablation of tumors is to induce apoptosis. Visualization of apoptosis during PDT in real-time is of great benefit for predicting and evaluating therapeutic outcomes. Herein, we engineered a highly stable and sensitive caspase-3 ferritin activatable probe (FABP/ZnPc) for simultaneous delivery of a photosensitizer (ZnPc) and real-time visualization of apoptosis during PDT. Upon near-infrared (NIR) light irradiation, ZnPc becomes active and initiates apoptosis, upon which the outer layer of the FABP/ZnPc is degraded by the apoptotic marker, caspase-3, to boost strong fluorescent signals, ultimately allowing real-time imaging of apoptosis. Our results demonstrate the utility of FABP/ZnPc as a tool for PDT and simultaneous imaging of caspase-3 activation in vitro and in vivo. Overall, the ability of FABP/ZnPc to image apoptosis during PDT will not only facilitate optimizing and personalizing the PDT strategy but is also important for understanding the mechanisms of PDT. PMID:26388178

  19. Illumination devices for uniform delivery of light to the oral cavity for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Canavesi, Cristina; Cassarly, William J.; Foster, Thomas H.; Rolland, Jannick P.

    2011-10-01

    To date, the lack of light delivery mechanisms to the oral cavity remains a barrier to the treatment of oral cancer with photodynamic therapy (PDT). The greatest impediment to medical practitioners is the current need to shield the normal tissues of the oral cavity, a costly and time-consuming procedure. In this research, we present the design of illumination devices to deliver light to the oral cavity for PDT, which will facilitate administration of PDT in the clinic. The goal for such an illumination device, as indicated by our clinical collaborators at Roswell Park Cancer Institute in Buffalo, NY, is to limit exposure of healthy tissue and produce an average irradiance of 100 mW/cm2 over the treatment field, with spatial non-uniformities below 10%. Furthermore, the size of the device must be compact to allow use in the oral cavity. Our research led to the design and fabrication of two devices producing spatial non-uniformities below 6% over a treatment area of 0.25 cm2 by design. One device consisted of an appropriately-sized reflector, inspired by solar concentrators, illuminated by a cylindrical diffusing fiber optimally located within the reflector; another was a solid lightpipe with a combination of optimized tapered and straight components.

  20. The evaluation and planning of light dose in photodynamic therapy for port wine stains

    NASA Astrophysics Data System (ADS)

    Zhang, Feng-juan; Hu, Xiaoming; Zhang, Qi-shen

    2014-11-01

    Photodynamic therapy (PDT) is one of the best available treatment for dermatology, especially for port wine stains (PWS), in which the efficacy is associated with the light dose, the photosensitizer concentration, the oxygen concentration and so on. Accurate control of the light dose will help doctors develop more effective treatment protocols, and reduce the treatment cost. Considering the characters of PWS, a binocular vision system composed of a camera, a digital projector and a computing unit is designed. An accurate 3D modeling of patients was achieved using a gray coding structured light, and then the lesions were segmented based on HSV space. Subsequently, each 3D point is fit on the surface by a nearest neighbor algorithm and the surface normal can be obtained. Three dimensional localization of lesion provide digital objective basis for automatic control of light device. The irradiance on the surface at a given angle can be assessed, and the optimum angle for the treatment can be solved and optimized by the doctor to improve irradiation areas.

  1. Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis.

    PubMed

    Zhang, Qian; Li, Zhuo-Heng; Li, Yuan-Yuan; Shi, San-Jun; Zhou, Shi-Wen; Fu, Yuan-Yuan; Zhang, Qing; Yang, Xue; Fu, Ruo-Qiu; Lu, Lai-Chun

    2015-01-01

    The conventional photosensitizers used in photodynamic therapy (PDT), such as haematoporphyrin (HP), have not yet reached satisfactory therapeutic effects on port-wine stains (PWSs), due largely to the long-term dark toxicity. Previously we have showed that hypericin exhibited potent photocytotoxic effects on Roman chicken cockscomb model of PWSs. However, the molecular mechanism of hypericin-mediated photocytotoxicity remains unclear. In this study, we employed human umbilical vein endothelial cells (HUVECs) to investigate the hypericin-photolytic mechanism. Our study showed that hypericin-PDT induced reactive oxygen species (ROS), resulting in cell killings and an activation of the inflammatory response. Importantly, we have also discovered that photoactivated hypericin induced apoptosis by activating the mitochondrial caspase pathway and inhibiting the activation of the vascular endothelial growth factor-A (VEGF-A)-mediated PI3K/Akt pathway. Notably, we found that hypericin exhibited a more potent photocytotoxic effect than HP, and largely addressed the inconvenience issue associated with the use of HP. Thereby, hypericin may be a better alternative to HP in treating PWSs. PMID:26673286

  2. Monitoring of cell and tissue responses to photodynamic therapy by electrical impedance spectroscopy

    NASA Astrophysics Data System (ADS)

    Molckovsky, A.; Wilson, B. C.

    2001-04-01

    Electrical impedance spectroscopic (EIS) monitoring of photodynamic therapy (PDT) was investigated in vivo in rat liver and in vitro in multicellular spheroids. Liver impedance was continuously measured with two needle electrodes before, during and up to 3 hours following Photofrin-PDT. EIS spectra were altered immediately after PDT, with significant changes in conductivity at ~10 kHz, and in permittivity at ~30 kHz and 1 MHz. The change in permittivity at high frequencies was related to oedema, while low-frequency effects were attributed to cell necrosis and vascular changes. Photofrin-PDT-treated spheroids showed dose-dependent decreases in permittivity and conductivity at frequencies above 10 and 100 kHz, respectively. Histology showed concomitant development of a damaged rim containing sparsely distributed cells with compromised membranes and lightly staining cytoplasm. Different EIS responses to apoptotic versus necrotic modes of cell death further verified the sensitivity of impedance to purely cellular changes in the spheroid model. In conclusion, EIS sensitivity to PDT-induced damage, at both the cell and tissue level, varies with dose and time, and can be correlated qualitatively to biological changes.

  3. Structural and Functional Outcomes in Chronic Central Serous Chorioretinopathy Treated with Photodynamic Therapy

    PubMed Central

    González, Eugenia; Asencio, Mónica; García, Jesús

    2015-01-01

    Purpose To study the retinal pigment epithelium (RPE) and retinal alterations in chronic central serous chorioretinopathy treated with photodynamic therapy, and its correlation with functional parameters such as best-corrected visual acuity (BCVA) and contrast sensitivity (CS). Methods Retrospective, noncomparative, consecutive evaluation by optical coherence tomography and its correlation with BCVA and CS in 31 eyes of 26 patients. Results In all affected patients, 88.5% were male with a mean age of 42.9 years. The right eye was involved in 64.5% of cases, bilateral in 19% and 73.9% were hyperopic (spherical refraction between 0 and +5.0 diopters). Of these cases, 51.5% had peri-RPE abnormalities, 17.3% hyperreflective substances at RPE, 19.4% RPE atrophy, 55.3% foveolar atrophy, 3.1% pigment epithelial detachment, 5.2% subretinal fluid persistence, 8.3% fibrin deposits, 68.4% photoreceptor inner and outer segment line interruption and 31.1% external limiting membrane interruption. Conclusions Time evolution and number of outbreaks were related to the decrease in foveal and chorodial thickness and in those with worse BCVA and CS. RPE abnormalities and atrophy were related to the age of onset of symptoms. Photoreceptor elongation has been correlated with poor BCVA and inner and outer segment line destructuring and interruption with poor CS. PMID:26457039

  4. Photodynamic therapy for early malignancies in the lower female genital tract

    NASA Astrophysics Data System (ADS)

    Lobraico, Rocco V.

    1990-09-01

    A total of 14 patients who had failed all conventional modalities for cancer of the vulva vagina and perianal area were treated with photodynamic therapy PDT. The affinity of porphyrins to neopJ. astic tissue enables treatment to be concentrated at the tumor site. An Aurora FL Argon pumped dye laser (Cooper LaserSonics Inc. USA) was used to pump dicyanomethylene dye as an activating source for a red light at a wavelength of 630 nm. The combination of a tumor localizing photosensitizer and photoactivating red light produces a photo chemical reaction that is destructive to the cancerous lesion. The treatment time varied between 10-30 minutes. Vulvar sites ranged from 9-38 cm2. Delivered light doses were from 50-125 J/cm2 and power density from 50 to 75 mW/cm2. A complete response was obtained in 80 of the sites treated as evidenced by negative biopsies taken at 3 months post treatment. Adverse reactions to PDT included a transient cutaneous photosensitivity due to retention of the photosensitizers in the skin. This reaction usually persisted from 45-60 days. 1.

  5. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

    PubMed

    Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

    2015-02-01

    Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type?I PDT process for enhanced antitumor therapeutic efficacy. PMID:25483028

  6. Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect

    NASA Astrophysics Data System (ADS)

    Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry

    2014-03-01

    PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20?W/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

  7. Fluorescence of Pc 4 in U87 cells following photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Varghai, Davood; Azizuddin, Kashif; Ahmad, Yusra; Oleinick, Nancy L.; Dean, David

    2007-02-01

    Introduction: Given the length of procedures and the brightness of operating room lights, there is concern that photosensitizers used to locate brain tumors and treat them with photodynamic therapy (PDT) may photobleach before they can be fully utilized. The phthalocyanine photosensitizer Pc 4 is resistant to photobleaching. In this study, we tested the hypothesis that exposure of Pc 4-loaded glioma cells to photoactivating light will result in continuing fluorescence of Pc 4. Methods: U87 human glioma cells were cultured in MEM with 5% penicillin/streptomycin, 5% sodium pyruvate, 10% fetal bovine serum, and 25 mM HEPES. These cultures were given 0 or 125 nM Pc 4, followed 2 hours later by three separate exposures of 200 J/cm2 of red light (? max = 675 nm). Confocal fluorescence images were collected before and after each exposure. Results: Pc 4 fluorescence was localized to cytoplasmic membranes of the U87 glioma cells, as previously seen in other types of cells. After exposure to PDT, Pc 4 fluorescence was not reduced and even increased. Discussion: Pc 4 may be useful for the intra-operative detection of glioma by fluorescence and for PDT, since neither Pc 4 level nor its fluorescence is likely to decrease during exposure to operating room lights.

  8. Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy

    PubMed Central

    Ben-Nun, Yael; Merquiol, Emmanuelle; Brandis, Alexander; Turk, Boris; Scherz, Avigdor; Blum, Galia

    2015-01-01

    Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cell killing by Photodynamic Therapy (PDT). These novel molecules are highly selective theranostic probes that enable both detection and treatment of cancer with minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated by light, resulting in oxidative stress and subsequent cell ablation, and a quencher that when removed by active cathepsins allow the PS to fluoresce and demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists of a selective cathepsin recognition sequence, a QC-1 quencher and a new bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non-invasive in vivo imaging of subcutaneous tumors and induced specific tumor macrophage apoptosis by light treatment, resulting in a substantial tumor shrinkage in an aggressive breast cancer mouse model. These results demonstrate for the first time that the PS-qABPs technology offers a functional theranostic tool, which can be applied to numerous tumor types and other inflammation-associated diseases. PMID:26000057

  9. CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

    2014-04-01

    The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

  10. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  11. Development and comparison of two devices for treatment of onychomycosis by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Silva, Ana Paula da; Chiandrone, Daniel José; Tinta, Jefferson Wanderson Rossi; Kurachi, Cristina; Inada, Natalia Mayumi; Bagnato, Vanderlei Salvador

    2015-06-01

    Onychomycosis is the most common nail disorder. The treatment for this type of infection is one of the main difficult ones in clinical practice, due to the fact that the nails are nonvascularized structures, which compromise the penetration of drugs delivered systemically and favor slow nail growth. We present two devices based on light-emitting diode arrays as light sources for the treatment of onychomycosis by photodynamic therapy (PDT). PDT is an emerging technique that uses a photosensitizer (PS) activated by light in the presence of oxygen. The PS absorbs energy from light and transfers it to oxygen, producing reactive oxygen species such as hydroxyl radicals, superoxide, and singlet oxygen which inactivate fungi and bacteria. Our proposal is the use of a portable and secure light source device in patients with onychomycosis. Additional advantages are the low cost involved, the possibility of topical treatment rather than systemic and the simplicity of operation. These advantages are important to ensure the implementation of this technology for the treatment of an impacting health problem.

  12. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

    PubMed Central

    Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-01-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•?), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•? and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

  13. Topical photodynamic therapy of squamous cell carcinomas in a hairless mouse model

    NASA Astrophysics Data System (ADS)

    Wang, Hong-Wei; Lv, Ting; Li, Jing-Jing; Tu, Qingfeng; Huang, Zheng; Wang, Xiu-Li

    2013-02-01

    Objectives: To examine therapeutic effects of 5-aminolevulinate (ALA)-mediated photodynamic therapy (PDT) on UVB-induced cutaneous squamous cell carcinomas (SCCs) in a mouse model. Materials and methods: Cutaneous SCCs were established by UVB (280-320 nm) irradiation of hairless mice. In situ fluorescence measurement was used to monitor PpIX formation after the topical application of various concentrations of ALA cream to determine the optimal ALA dose. Therapeutic responses of SCCs to multiple sessions of ALA PDT were examined histologically and quantitatively. TUNEL staining was used to examine apoptosis caused by PDT. Results: After repeated exposure for 18 to 22 weeks (4-5 days/week), multiple nodular and verrucous hyperplasia lesions of various sizes developed at the exposed area. After four sessions of ALA PDT (8% ALA, 3 h incubation, 30 J/cm2 at 20 mW/cm2) a total of 84% of complete response was achieved for small SCCs (1-4 mm, thickness <2.5 mm). TUNEL staining showed that PDT-induced apoptotic cells were distributed evenly from the basal to stratum corneum layers. Conclusions: Topical ALA PDT can trigger apoptosis in SCCs, inhibit SCC growth, and reduce the size and number of tumors in the hairless mouse model. The true clinical value of ALA PDT for the treatment of cutaneous SCC deserves further investigation.

  14. Assessment of Rose Bengal vs. Riboflavin Photodynamic Therapy for Inhibition of Fungal Keratitis Isolates

    PubMed Central

    Arboleda, Alejandro; Miller, Darlene; Cabot, Florence; Taneja, Mukesh; Aguilar, Mariela C.; Alawa, Karam; Amescua, Guillermo; Yoo, Sonia H.; Parel, Jean-Marie

    2014-01-01

    Purpose To compare the in vitro effect of rose bengal and riboflavin as photosensitizing agents for photodynamic therapy (PDT) on fungal isolates that are common causes of fungal keratitis Design Experimental study Methods Three isolates (Fusarium solani, Aspergillus fumigatus, Candida albicans) recovered from patients with confirmed fungal keratitis were used in the experiments. Isolates were grown on Sabouraud-Dextrose agar, swabbed and prepared in suspension, and one milliliter aliquots were inoculated onto test plates in triplicate. Test plates were separated into 5 groups: Group 1 - no treatment, Group 2 - 0.1% rose bengal alone, Group 3 - 518 nm irradiation alone, Group 4 - riboflavin PDT (riboflavin + 375 nm irradiation), and Group 5 - rose bengal PDT (rose bengal + 518 nm irradiation). Irradiation was performed over a circular area using either a green LED array (peak wavelength: 518 nm) or a UV-A LED array (peak wavelength: 375 nm). Test plates were irradiated with an energy density of 5.4 J/cm2. Later, plates were placed in a 30° C incubator and observed for growth. Results Rose bengal-mediated PDT successfully inhibited the growth of all three fungal isolates in the irradiated area. All other groups exhibited unrestricted growth throughout the plate. Conclusions Rose bengal-mediated PDT successfully inhibited the growth of three types of fungi. No other experimental groups, including riboflavin-mediated PDT, had any inhibitory effect on the isolates. The results might be useful for the treatment of patients suffering from corneal infection. PMID:24792103

  15. Photodynamic therapy (PDT) to treat a chronic skin wound in a dog

    NASA Astrophysics Data System (ADS)

    Hage, Raduan; Plapler, Hélio; Bitar, Renata A.

    2008-02-01

    Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.

  16. Photodynamic Therapy: Occupational Hazards and Preventative Recommendations for Clinical Administration by Healthcare Providers

    PubMed Central

    Lacey, Steven E.; Vesper, Benjamin J.; Paradise, William A.; Radosevich, James A.; Colvard, Michael D.

    2013-01-01

    Abstract Objective: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. Materials and methods: Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. Results: Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. Conclusions: Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies. PMID:23859750

  17. Preparation and characterization of mTHPC-loaded solid lipid nanoparticles for photodynamic therapy.

    PubMed

    Navarro, Fabrice P; Creusat, Gaëlle; Frochot, Céline; Moussaron, Albert; Verhille, Marc; Vanderesse, Régis; Thomann, Jean-Sébastien; Boisseau, Patrick; Texier, Isabelle; Couffin, Anne-Claude; Barberi-Heyob, Muriel

    2014-01-01

    Among various attempts to enhance the therapeutic efficacy of photodynamic therapy (PDT), the specific delivery of photosensitizer (PS) in the tumor tissue is expected to improve its clinical applications. The aim of this study was to engineer lipid nanoparticles (LNP) with different sizes and various PS contents, using simple solvent-free and easily scale up manufacturing processes. Meso-(tetrahydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive compounds for clinical use. We demonstrated that mTHPC was efficiently incorporated into the lipid core of LNP, leading to a large range of stable and reproducible mTHPC-loaded LNP with narrow size distribution. Photophysical and physico-chemical properties of mTHPC-loaded LNP were assessed as well as absorption spectra and singlet oxygen emission, colloidal stability, particle size and zeta potential. The photocytotoxicity of selected mTHPC-loaded solid LNP was demonstrated on MCF-7 cells under irradiation at 652nm with a range of light fluence from 1.0 to 10J/cm(2). All physico-chemical, photophysical and biological results allow us to conclude that solid LNP appear as a very promising nano-mTHPC delivery system for PDT. PMID:24333764

  18. In vitro study on methemoglobin formation in erythrocytes following hexyl-aminolevulinate induced photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2007-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as hexyl-aminolevulinate (HAL) may increase the efficiency of PDT. HAL penetrates into the cell where the photosensitizer protoporphyrin IX (PPIX) is produced endogenously. In a previous study on HAL based PDT treatment of rat bladder cancer (AY-27 transitional cell carcinoma), a depression of the optical reflectance spectra after treatment was observed in some of the animals. This depression of the spectra was caused by metHemoglobin (metHb). MetHb is an indication of oxidative stress, and can be formed as a result of for instance UV-radiation and heating of blood. The aim of this study was to identify if metHb can be formed in vitro as a result of oxidative stress caused by singlet oxygen and ROS produced during PDT. Methemoglobin formed during PDT might thus be used as an indirect measure of the photochemical processes. This may help predict the PDT treatment outcome. Red blood cells mixed with AY-27 cells exposed to HAL, or PPIX received light treatment, and the changes in the absorption spectra were measured spectrophotometrically. The methemoglobin absorbance spectrum was also studied, and found to be strongly dependant on pH. Hemolysis of erythrocytes by PDT was found, however no metHb was formed in vitro.

  19. Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis

    PubMed Central

    Zhang, Qian; Li, Zhuo-heng; Li, Yuan-yuan; Shi, San-jun; Zhou, Shi-wen; Fu, Yuan-yuan; Zhang, Qing; Yang, Xue; Fu, Ruo-qiu; Lu, Lai-chun

    2015-01-01

    The conventional photosensitizers used in photodynamic therapy (PDT), such as haematoporphyrin (HP), have not yet reached satisfactory therapeutic effects on port-wine stains (PWSs), due largely to the long-term dark toxicity. Previously we have showed that hypericin exhibited potent photocytotoxic effects on Roman chicken cockscomb model of PWSs. However, the molecular mechanism of hypericin-mediated photocytotoxicity remains unclear. In this study, we employed human umbilical vein endothelial cells (HUVECs) to investigate the hypericin-photolytic mechanism. Our study showed that hypericin-PDT induced reactive oxygen species (ROS), resulting in cell killings and an activation of the inflammatory response. Importantly, we have also discovered that photoactivated hypericin induced apoptosis by activating the mitochondrial caspase pathway and inhibiting the activation of the vascular endothelial growth factor-A (VEGF-A)-mediated PI3K/Akt pathway. Notably, we found that hypericin exhibited a more potent photocytotoxic effect than HP, and largely addressed the inconvenience issue associated with the use of HP. Thereby, hypericin may be a better alternative to HP in treating PWSs. PMID:26673286

  20. Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

    2015-05-01

    There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ?50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

  1. Clinical trials of a new chlorin photosensitizer for photodynamic therapy of malignant tumors

    NASA Astrophysics Data System (ADS)

    Privalov, Valeriy A.; Lappa, Alexander V.; Seliverstov, Oleg V.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.; Kochneva, Elena V.; Evnevich, Michail V.; Anikina, Alla S.; Reshetnicov, Andrey V.; Zalevsky, Igor D.; Kemov, Yuriy V.

    2002-06-01

    Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and efficiency of it. PDT was applied to 51 patients with basal cell cancer of the skin (about 60% of all cases), breast cancer, lip cancer, melanoma, cancer of esophagus, stomach, and rectum, cancer and leucoplacia of vulva, malignant ganglioneuroma, sarcoma of soft tissue, cancer and reticular sarcoma of thyroid gland, cancer of ductus choledochus. Most of non-basalioma patients had either forth stage or recurrence of disease. The sensitizer was injected intravenously or applied externally (Radachlorin gel). There were used surface, endoscopic, and interstitial ways of irradiation. Full tumor regression with excellent cosmetic effect was reached in 100% cases of 1-3 stage basal cell cancer patients treated with intravenous Radachlorin injection. In most other (non-basalioma) cases significant regression of tumors and improvement of life quality of patients (recanalization and regain of conductivity) was obtained.

  2. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    NASA Astrophysics Data System (ADS)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-?) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-? and 2-? activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-? cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-? PDT of AMD.

  3. Photodynamic therapy (PDT) of endometrium primary cultures serving as an in-vitro model for endometriosis

    NASA Astrophysics Data System (ADS)

    Herter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  4. Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

    PubMed Central

    Fingar, V H; Kik, P K; Haydon, P S; Cerrito, P B; Tseng, M; Abang, E; Wieman, T J

    1999-01-01

    Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg?1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm?2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. © 1999 Cancer Research Campaign PMID:10206280

  5. A medical manipulator system with lasers in photodynamic therapy of port wine stains.

    PubMed

    Wang, Xingtao; Tian, Chunlai; Duan, Xingguang; Gu, Ying; Huang, Naiyan

    2014-01-01

    Port wine stains (PWS) are a congenital malformation and dilation of the superficial dermal capillary. Photodynamic therapy (PDT) with lasers is an effective treatment of PWS with good results. However, because the laser density is uneven and nonuniform, the treatment is carried out manually by a doctor thus providing little accuracy. Additionally, since the treatment of a single lesion can take between 30 and 60 minutes, the doctor can become fatigued after only a few applications. To assist the medical staff with this treatment method, a medical manipulator system (MMS) was built to operate the lasers. The manipulator holds the laser fiber and, using a combination of active and passive joints, the fiber can be operated automatically. In addition to the control input from the doctor over a human-computer interface, information from a binocular vision system is used to guide and supervise the operation. Clinical results are compared in nonparametric values between treatments with and without the use of the MMS. The MMS, which can significantly reduce the workload of doctors and improve the uniformity of laser irradiation, was safely and helpfully applied in PDT treatment of PWS with good therapeutic results. PMID:25302297

  6. Microgel-Encapsulated Methylene Blue for the Treatment of Breast Cancer Cells by Photodynamic Therapy

    PubMed Central

    Khanal, Anil; Bui, Minh-Phuong Ngoc

    2014-01-01

    Purpose Photodynamic therapy (PDT) is gaining increasing recognition for breast cancer treatment because it offers local selectivity and reduced toxic side effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs are loaded in different nanomaterials and used in combination with light exposure. However, the most representative issue with PDT is the difficulty of nanomaterials to encapsulate anticancer drugs at high doses, which results in low efficacy of the PDT treatment. Here, we proposed the development of the poly(N-isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue, an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line. Methods We developed biocompatible microgels based on nonfunctionalized PNIPAM and its corresponding anionically functionalized PNIPAM and polyacrylic acid (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug because of its ability to generate toxic reactive oxygen species upon exposure to light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were synthesized and characterized using ultraviolet-visible spectroscopy and dynamic light scattering. The effect of methylene blue was evaluated using the MCF-7 cell line. Results Loading of methylene blue in core PNIPAM microgel was higher than that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic interactions did not play an important role in loading a cationic drug. This behavior is probably due to the skin layer inhibiting the high uptake of drugs in the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the cationic drug (i.e., methylene blue) for several hours compared to core/shell PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of free methylene blue. Conclusion Our results showed that the employment of core PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of methylene blue. Core PNIPAM microgel released the drug more slowly than did core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells. PMID:24744793

  7. Adjuvant therapy of melanoma with interferon: lessons of the past decade

    PubMed Central

    Ascierto, Paolo A; Kirkwood, John M

    2008-01-01

    The effect of interferon alpha (IFN?2) given alone or in combination has been widely explored in clinical trials over the past 30 years. Despite the number of adjuvant studies that have been conducted, controversy remains in the oncology community regarding the role of this treatment. Recently an individual patient data (IPD) meta-analysis at longer follow-up was reported, showing a statistically significant benefit for IFN in relation to relapse-free survival, without any difference according to dosage (p = 0.2) or duration of IFN therapy (p = 0.5). Most interestingly, there was a statistically significant benefit of IFN upon overall survival (OS) that translates into an absolute benefit of at least 3% (CI 1–5%) at 5 years. Thus, both the individual trials and this meta-analysis provide evidence that adjuvant IFN?2 significantly reduces the risk of relapse and mortality of high-risk melanoma, albeit with a relatively small absolute improvement in survival in the overall population. We have surveyed the international literature from the meta-analysis (2006) to summarize and assimilate current biological evidence that indicates a potent impact of this molecule upon the tumor microenvironment and STAT signaling, as well as the immunological polarization of the tumor tissue in vivo. In conclusion, we argue that there is a compelling rationale for new research upon IFN, especially in the adjuvant setting where the most pronounced effects of this agent have been discovered. These efforts have already shed light upon the immunological and proinflammatory predictors of therapeutic benefit from this agent – that may allow practitioners to determine which patients may benefit from IFN therapy, and approaches that may enable us to overcome resistance or enhance the efficacy of IFN. Future efforts may well build toward patient-oriented therapy based upon the knowledge of the unique molecular features of this disease and the immune system of each melanoma patient. PMID:18954464

  8. In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform

    NASA Astrophysics Data System (ADS)

    Liu, Xiaomin; Que, Ivo; Kong, Xianggui; Zhang, Youlin; Tu, Langping; Chang, Yulei; Wang, Tong Tong; Chan, Alan; Löwik, Clemens W. G. M.; Zhang, Hong

    2015-09-01

    A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, 1O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm-2) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy.A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, 1O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm-2) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03690a

  9. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    SciTech Connect

    Li Baoqing; Chen, Margaret; Nori, Dattatreyudu; Chao, K.S. Clifford; Chen, Allen M.; Chen, Steven L.

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is important. Adjuvant radiation can be omitted for patients older than 65.

  10. Photodynamic Therapy of the Canine Prostate: Intra-arterial Drug Delivery

    SciTech Connect

    Moore, Ronald B. Xiao, Zhengwen; Owen, Richard J.; Ashforth, Robert; Dickey, Dwayne; Helps, Cathy; Tulip, John

    2008-01-15

    Purpose. Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method-intra-arterial drug delivery for PDT of the prostate-in a canine model.Methods. To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ({sup 99m}Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. Results. Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of {sup 99m}Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. Conclusion. Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.

  11. Metronomic photodynamic therapy (mPDT): concepts and technical feasibility in brain tumor

    NASA Astrophysics Data System (ADS)

    Wilson, Brian C.; Bisland, Stuart K.; Bogaards, Arjen; Lin, Annie; Moriyama, Eduardo H.; Zhang, Kai; Lilge, Lothar D.

    2003-06-01

    The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates over extended periods in order to increase selective tumor cell kill through apoptosis. The focus of the present work is on mPDT treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. In order to produce enough tumor cell kill to be an effective therapy, multiple PDT treatments, such as hyperfractionation or metronomic delivery, are likely requried, based on the levels of apoptosis achieved and model calculations of tumor growth rates. mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery while allowing free movement. In rat models ALA administration via the drinking water has been accomplished at significant doses for up to 10 days, and ex vivo spectrofluorimetry of tumore, normal brain and other tissues post mortem demonstrates a 3-4 increase in the tumor-to-brain concentration of PpIX, without toxicity. Prototype light sources and delivery devices are also shown to be practical, either using a laser diode or light emitting diode (LED) coupled to an implanted optical fiber in the case of the rat model or a directly-implanted LED in rabbits. The combined delivery of both drug and light over an extended period, with survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.

  12. Metronomic photodynamic therapy (mPDT) for intracranial neoplasm: physiological, biological, and dosimetry considerations

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart L.; Lilge, Lothar; Lin, Annie; Wilson, Brian C.

    2003-10-01

    Metronomic photodynamic therapy (mPDT), a procedure in which both the photosensitizer and light are delivered continuously so that the individual doses overlap pharmacologically is introduced. The fundamental hypothesis in mPDT is that by providing therapy at low fluence over extended periods of time, there is potential for improved selectivity in tumor cell kill through non necrotic pathways. This is especially important in the treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PiIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue nor apoptosis in the latter. However, in order to achieve tumor control, multiple PDT treatments, such as hyper fractionation or metronomic delivery, are required, where the frequency and duration of the treatment are determined by the levels of apoptosis achieved in relationship to tumor cell doubling times, mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery at a sufficiently high enough density to achieve low fluence exposure to the brain adjacent to tumor or the entire hemisphere. In a rat model we evaluated the feasibility of delivering sustained ALA administration via the drinking water for up to 10 days without loss of PPIX selectivity. Post mortem quantitative spectrofluorimetry of tumor, normal brain and other tissues demonstrates a 4 times higher PPIX concentration in the 9L gliosarcoma model without noticeable toxicity. Light sources and delivery devices based either on laser diode or light emitting diode (LED) coupled to an implanted optical fiber were shown to be feasible. The maximum permissible spacing of cylindrical isotropic emitters is determined using known apoptotic indices and the necrosis threshold value for white matter. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.

  13. Monte Carlo fluence simulation for prospective evaluation of interstitial photodynamic therapy treatment plans

    NASA Astrophysics Data System (ADS)

    Cassidy, Jeffrey; Betz, Vaughn; Lilge, Lothar

    2015-03-01

    Photodynamic therapy (PDT) delivers a localized cytotoxic dose that is a function of tissue oxygen availability, photosensitive drug concentration, and light fluence. Providing safe and effective PDT requires an understanding of all three elements and the physiological response to the radicals generated. Interstitial PDT (IPDT) for solid tumours poses particular challenges due to complex organ geometries and the associated limitations for diffusion theory based fluence rate prediction, in addition to restricted access for light delivery and dose monitoring. As a first step towards enabling a complete prospective IPDT treatment-planning platform, we demonstrate use of our previously developed FullMonte tetrahedral Monte Carlo simulation engine for modeling of the interstitial fluence field due to intravesicular insertion of brief light sources. The goal is to enable a complete treatment planning and monitoring work flow analogous to that used in ionizing radiation therapy, including plan evaluation through dose-volume histograms and algorithmic treatment plan optimization. FullMonte is to our knowledge the fastest open-source tetrahedral MC light propagation software. Using custom hardware acceleration, we achieve 4x faster computing with 67x better power efficiency for limited-size meshes compared to the software. Ongoing work will improve the performance advantage to 16x with unlimited mesh size, enabling algorithmic plan optimization in reasonable time. Using FullMonte, we demonstrate significant new plan-evaluation capabilities including fluence field visualization, generation of organ dose-volume histograms, and rendering of isofluence surfaces for a representative bladder cancer mesh from a real patient. We also discuss the advantages of MC simulations for dose-volume histogram generation and the need for online personalized fluence-rate monitoring.

  14. Early photosensitizer uptake kinetics predict optimum drug-light interval for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sinha, Lagnojita; Elliott, Jonathan T.; Hasan, Tayyaba; Pogue, Brian W.; Samkoe, Kimberley S.; Tichauer, Kenneth M.

    2015-03-01

    Photodynamic therapy (PDT) has shown promising results in targeted treatment of cancerous cells by developing localized toxicity with the help of light induced generation of reactive molecular species. The efficiency of this therapy depends on the product of the intensity of light dose and the concentration of photosensitizer (PS) in the region of interest (ROI). On account of this, the dynamic and variable nature of PS delivery and retention depends on many physiological factors that are known to be heterogeneous within and amongst tumors (e.g., blood flow, blood volume, vascular permeability, and lymph drainage rate). This presents a major challenge with respect to how the optimal time and interval of light delivery is chosen, which ideally would be when the concentration of PS molecule is at its maximum in the ROI. In this paper, a predictive algorithm is developed that takes into consideration the variability and dynamic nature of PS distribution in the body on a region-by-region basis and provides an estimate of the optimum time when the PS concentration will be maximum in the ROI. The advantage of the algorithm lies in the fact that it predicts the time in advance as it takes only a sample of initial data points (~12 min) as input. The optimum time calculated using the algorithm estimated a maximum dose that was only 0.58 +/- 1.92% under the true maximum dose compared to a mean dose error of 39.85 +/- 6.45% if a 1 h optimal light deliver time was assumed for patients with different efflux rate constants of the PS, assuming they have the same plasma function. Therefore, if the uptake values of PS for the blood and the ROI is known for only first 12 minutes, the entire curve along with the optimum time of light radiation can be predicted with the help of this algorithm.

  15. Imiquimod immunotherapy and ALA photodynamic therapy combination for the treatment of genital bowenoid papulosis

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Guo, Ming-Xia; Huang, Zheng

    2007-02-01

    To investigate the feasibility and efficacy of combination of imiquimod immunotherapy and 5- aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for the treatment of genital bowenoid papulosis (BP). A total of twenty seven BP patients were randomized into two groups: (I) fifteen patients (12 male and 3 female, age 22-56 years old) were treated with topical application of 5% imiquimod cream (three times a week) and ALA-PDT (100 J/cm2 at 100 mW/cm2, once a week) for 1-4 times in one week interval. (II) Twelve patients (6 male and 6 female, age 29-58 years old) were treated with CO II laser vaporization as a control. Patients were followed up for 3 to 12 months. Results: In combined therapy group, 60% (9/15) patients showed complete remission and only one recurred (11.1%) during follow up. Local side effects included mild erythema, edema, erosion and burning and/or stinging sensation. No systemic side effect was found. In CO II laser vaporization group, 83.3% (10/12) patients showed complete remission. However, recurrence occurred in 6 patients (60.0%). Local side effects included mild to moderate edema, erosion, ulceration, delayed healing, prolonged pain and scarring. The difference of recurrence rate between two groups was statistically significant (P < 0.05). Topical application of imiquimod cream and ALA-PDT is safe, effective and associated with low recurrence and less side effect. Its true clinical value needs to be further investigated by a long-term follow-up of large scale trial.

  16. ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Peng, Qian; Sun, Chung-Ho; Sorensen, Dag R.; Carper, Steven W.; Madsen, Steen J.

    2005-04-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.

  17. Benzoporphyrin derivative and light-emitting diode for use in photodynamic therapy: Applications of space light-emitting diode technology

    SciTech Connect

    Whelan, Harry T.; Houle, John M.; Bajic, Dawn M.; Schmidt, Meic H.; Reichert, Kenneth W. II; Meyer, Glenn A.

    1998-01-15

    Photodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for brain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor cells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation followed by cell death. The development of more effective light sources for PDT of brain tumors has been facilitated by applications of space light-emitting diode array technology; thus permitting deeper tumor penetration of light and use of better photosensitizers. Currently, the most commonly used photosensitizer for brain tumor PDT is Photofrin registered . Photofrin registered is a heterogeneous mixture of compounds derived from hematoporphyrin. Photofrin registered is activated with a 630 nm laser light and does destroy tumor cells in animal models and humans. However, treatment failure does occur using this method. Most investigators attribute this failure to the limited penetration of brain tissue by a 630 nm laser light and to the fact that Photofrin registered has only a minor absorption peak at 630 nm, meaning that only a small fraction of the chemical is activated. Benzoporphyrin Derivative Monoacid Ring A (BPD) is a new, second generation photosensitizer that can potentially improve PDT for brain tumors. BPD has a major absorption peak at 690 nm, which gives it two distinct advantages over Photofrin registered . First, longer wavelengths of light penetrate brain tissue more easily so that larger tumors could be treated, and second, the major absorption peak means that a larger fraction of the drug is activated upon exposure to light. In the first part of this project we have studied the tumoricidal effects of BPD in vitro using 2A9 canine glioma and U373 human glioblastoma cell cultures. Using light emitting diodes (LED) with a peak emission of 688 nm as a light source, cell kill of up to 86 percent was measured in these cell lines by tumor DNA synthesis reduction. The effectiveness of BPD against tumor cells in vitro thus established, we have taken the first step toward determining its effectiveness in vivo. The second part of this project consisted of experiments performed to determine the maximum tolerated dose (MTD) of both BPD and LED light. At a light dose of 100 J/cm{sup 2}, skin damage and neurotoxicity were seen at a BPD dose of 1.0 mg/kg, but not at a dose of 0.75 mg/kg. When BPD remained constant at 0.75 mg/kg, skin damage was seen at light dosages of 125 J/cm{sup 2}, 150 J/cm{sup 2} and 175 J/cm{sup 2}. One dog also died at a light dose of 175 J/cm{sup 2}. Further studies will be needed to determine the effectiveness of BPD against tumor cells in vivo.

  18. Benzoporphyrin derivative and light-emitting diode for use in photodynamic therapy: Applications of space light-emitting diode technology

    NASA Astrophysics Data System (ADS)

    Whelan, Harry T.; Houle, John M.; Bajic, Dawn M.; Schmidt, Meic H.; Reichert, Kenneth W.; Meyer, Glenn A.

    1998-01-01

    Photodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for brain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor cells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation followed by cell death. The development of more effective light sources for PDT of brain tumors has been facilitated by applications of space light-emitting diode array technology; thus permitting deeper tumor penetration of light and use of better photosensitizers. Currently, the most commonly used photosensitizer for brain tumor PDT is Photofrin®. Photofrin® is a heterogeneous mixture of compounds derived from hematoporphyrin. Photofrin® is activated with a 630 nm laser light and does destroy tumor cells in animal models and humans. However, treatment failure does occur using this method. Most investigators attribute this failure to the limited penetration of brain tissue by a 630 nm laser light and to the fact that Photofrin® has only a minor absorption peak at 630 nm, meaning that only a small fraction of the chemical is activated. Benzoporphyrin Derivative Monoacid Ring A (BPD) is a new, second generation photosensitizer that can potentially improve PDT for brain tumors. BPD has a major absorption peak at 690 nm, which gives it two distinct advantages over Photofrin®. First, longer wavelengths of light penetrate brain tissue more easily so that larger tumors could be treated, and second, the major absorption peak means that a larger fraction of the drug is activated upon exposure to light. In the first part of this project we have studied the tumoricidal effects of BPD in vitro using 2A9 canine glioma and U373 human glioblastoma cell cultures. Using light emitting diodes (LED) with a peak emission of 688 nm as a light source, cell kill of up to 86 percent was measured in these cell lines by tumor DNA synthesis reduction. The effectiveness of BPD against tumor cells in vitro thus established, we have taken the first step toward determining its effectiveness in vivo. The second part of this project consisted of experiments performed to determine the maximum tolerated dose (MTD) of both BPD and LED light. At a light dose of 100 J/cm2, skin damage and neurotoxicity were seen at a BPD dose of 1.0 mg/kg, but not at a dose of 0.75 mg/kg. When BPD remained constant at 0.75 mg/kg, skin damage was seen at light dosages of 125 J/cm2, 150 J/cm2 and 175 J/cm2. One dog also died at a light dose of 175 J/cm2. Further studies will be needed to determine the effectiveness of BPD against tumor cells in vivo.

  19. Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy.

    PubMed

    Hofman, Jan-Willem; van Zeeland, Femke; Turker, Selcan; Talsma, Herre; Lambrechts, Saskia A G; Sakharov, Dmitri V; Hennink, Wim E; van Nostrum, Cornelus F

    2007-04-01

    Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, were synthesized and their tendency to aggregate as well as their photodynamic properties in 14C and B16F10 cell lines were evaluated. The results were compared to more hydrophilic silicon Pcs, that is, Si(PEG750)2Pc and Pc4. The order of cellular uptake was Pc4 > ZnPc(sol)8 > Si(PEG750)2Pc > Si(sol2)Pc. In contrast, Si(sol2)Pc showed the highest photocytotoxicity, while ZnPc(sol)8 did not show any photocytotoxicity up to a concentration of 10 microM in both cell types. UV/vis spectroscopy showed that Si(sol)2Pc is less prone to aggregation than ZnPc(sol)8, which can explain the lack of photoactivity of the latter. Si(sol)2Pc was predominantly located in lipid droplets, whereas Si(PEG750)2Pc was homogeneously distributed in the cytosol, which is probably the main cause of their difference in photoactivity. The very high photodynamic efficacy of Si(sol)2Pc makes this PS an interesting candidate for future studies. PMID:17348640

  20. Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy

    PubMed Central

    Zheng, Yuanhong; Yin, Guifang; Le, Vanminh; Zhang, Anle; Chen, Siyu; Liang, Xin; Liu, Jianwen

    2016-01-01

    Photodynamic therapy (PDT), a regulatory approved cancer treatment, is reported to be capable of causing immunogenic apoptosis. The current data reveal PDT can cause the dysregulation of “eat me” and “don't eat me” signal by generating reactive oxygen species (ROS) -mediated endoplasmic reticulum (ER) stress. This dysregulation probably contribute to the increased uptake of PDT-killed Lewis lung carcinoma (LLC) cells by homologous dendritic cells (DCs), accompanied by phenotypic maturation (CD80high, CD86high, and CD40high) and functional stimulation (NOhigh, IL-10absent) of dendritic cells as well as subsequent T-cell responses. Morevover, C57BL/6 mice vaccinated with dendritic cells (DCs) pulsed with PDT-treated LLCs (PDT-DCs) or PDT-treated LLCs alone (PDT-LLCs) exhibited potent immunity against LLC tumors. In the current study, the PDT-induced immune response was characterized as a process related with the dysregulation of “eat me” signal and “don't eat me” signal, revealing the possibility for developing PDT into an antitumor vaccination strategy for personalized cancer immunotherapy. PMID:26722223

  1. Combined Intravitreal Anti-VEGF and Photodynamic Therapy versus Photodynamic Monotherapy for Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis of Comparative Studies

    PubMed Central

    Wang, Wei; He, Miao; Zhang, Xiulan

    2014-01-01

    Purpose The aim of this study was to evaluate the efficacy and safety of photodynamic therapy (PDT) combined with intravitreal vascular endothelial growth factor (VEGF) inhibitors compared to those of PDT alone in the treatment of polypoidal choroidal vasculopathy (PCV). Methods A systematic search of Pubmed, Embase, and the Cochrane Library was performed to identify all comparative studies that compared the outcomes of the two approaches. Outcomes of interest included visual outcomes, anatomic variables, and adverse events. Results Two randomised controlled trials and nine retrospective studies including a total of 543 cases were identified. At three and six months post-injection, no significant difference in visual acuity was found in the combined therapy group compared with the PDT monotherapy group, with pooled weighted mean differences (WMDs) of 0.074 (?0.021, 0.17) at three months and 0.082 (?0.013, 0.18) at six months. However, the mean changes in visual acuity at month 12 in the combined therapy group were significantly better than those in the PDT monotherapy group, with pooled WMDs of 0.11 (0.012, 0.21). Similar efficacy was found at 24 months (WMD: 0.21; 95%CI: 0.054, 0.36; P?=?0.008). Patients in the combined therapy group also might benefit from reduced retinal haemorrhage (OR: 0.32; 95% CI: 0.14, 0.74; P?=?0.008). Polyp regression, recurrence of PCV, central retinal thickness reduction, and pigment epithelial detachment resolution did not differ significantly between the two treatments. Conclusions Combined treatment appeared to result in better visual acuity and lower retinal haemorrhage. However, combined treatment did not affect the resolution and recurrence of lesions. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update the findings of this analysis. PMID:25343244

  2. Fracture Risk and Adjuvant Therapies in Young Breast Cancer Patients: A Population-Based Study

    PubMed Central

    Chang, Chun-Hung; Chen, Shaw-Ji; Liu, Chieh-Yu

    2015-01-01

    Background Breast cancer survivors have an increased risk of bone fracture. But the risk among young patients with adjuvant therapies remains unknown. This population-based study is aimed to assess the incidence and risk of fracture among young (age of 20 to 39 years) breast cancer patients who received adjuvant therapies. Methods From January 2001 to December 2007, 5,146 newly diagnosed breast cancer patients were enrolled from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients were observed for a maximum of 6 years to determine the incidence of newly onset fracture. Kaplan Meier and Cox regression analyses were used to evaluate the risk of fracture in young breast cancer patients who received adjuvant treatments. Results Of the total 5,146 young (age of 20 to 39 years) breast cancer patients, the Cox multivariate proportional hazards analysis showed that AIs, radiotherapy, and monoclonal antibodies were significantly associated with a high risk of fracture. Moreover, patients who received AIs for more than 180 days had a high hazard ratio (HR) of 1.77 (95% CI = 0.68–4.57), and patients who received more than four radiotherapy visits had a high HR of 2.54 (95% CI = 1.07–6.06). Under the site-specific analysis, young breast cancer patients who received AIs had the highest risk of hip fracture (HR = 8.520, 95% CI = 1.711–42.432, p < 0.04), whereas patients who received radiotherapy had the highest risk of vertebral fracture (HR = 5.512, 95% CI = 1.847–16.451, p < 0.01). Conclusion Young breast cancer patients who are receiving AIs, radiotherapy or monoclonal antibody need to be more careful for preventing fracture events. Breast cancer treatment plans are suggested to incorporate fracture prevention interventions. PMID:26107848

  3. Comparison of Photodynamic Therapy versus conventional antifungal therapy for the treatment of denture stomatitis: a randomized clinical trial.

    PubMed

    Mima, E G; Vergani, C E; Machado, A L; Massucato, E M S; Colombo, A L; Bagnato, V S; Pavarina, A C

    2012-10-01

    In this randomized clinical trial, the clinical and mycological efficacy of Photodynamic Therapy (PDT) was compared with that of topical antifungal therapy for the treatment of denture stomatitis (DS) and the prevalence of Candida species was identified. Patients were randomly assigned to one of two groups (n = 20 each); in the nystatin (NYT) group patients received topical treatment with nystatin (100,000 IU) four times daily for 15 days and in the PDT group the denture and palate of patients were sprayed with 500 mg/L of Photogem(®), and after 30 min of incubation, were illuminated by light emitting-diode light at 455 nm (37.5 and 122 J/cm(2), respectively) three times a week for 15 days. Mycological cultures taken from dentures and palates and standard photographs of the palates were taken at baseline (day 0), at the end of the treatment (day 15) and at the follow-up time intervals (days 30, 60 and 90). Colonies were quantified (CFU/mL) and identified by biochemical tests. Data were analysed by Fisher's exact test, analysis of variance and Tukey tests and ? test (? = 0.05). Both treatments significantly reduced the CFU/mL at the end of the treatments and on day 30 of the follow-up period (p <0.05). The NYT and PDT groups showed clinical success rates of 53% and 45%, respectively. Candida albicans was the most prevalent species identified. PDT was as effective as topical nystatin in the treatment of DS. PMID:22731617

  4. Adjuvant Systemic Therapy in Older Breast Cancer Women: Can We Optimize the Level of Care?

    PubMed Central

    Mislang, Anna Rachelle; Biganzoli, Laura

    2015-01-01

    Defining optimal adjuvant treatment for older women with breast cancer is challenged by the lack of level-1 clinical evidence and the heterogeneity of the older population. Nevertheless, recommendations based on reviews of available evidence mainly from retrospective subgroup analyses and extrapolation of study results from younger patients, and expert opinions, may be useful to guide treatment decisions in fit patients. But how can we properly define a “fit” older patient? In clinical practice, age by itself and clinical impression generally drive treatment decision, although the appropriateness of this judgment is under-documented. Such an approach risks overtreatment or, more frequently, undertreatment. A geriatric assessment can be valuable in oncology practice to address this issue. In this review article, we will focus only on systemic treatment and will discuss “standard” adjuvant systemic treatment strategies for fit older breast cancer patients and the role of “personalized” systemic therapy in unfit patients. The concepts conveyed in this review cannot be extrapolated to locoregional therapy. PMID:26151681

  5. Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

    PubMed Central

    Jordan, V. Craig

    2014-01-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

  6. Adjuvant hormonal therapy in premenopausal women with operable breast cancer: not-so-peripheral perspectives.

    PubMed

    Love, Richard R

    2010-04-15

    Reviews of issues around adjuvant hormonal therapies for breast cancer in premenopausal women often focus on recent and current large clinical trials, and fail to address other subjects that are very germane to evidence-based and investigatory clinical practice. These topics include: (1) the descriptive epidemiology of breast cancer globally, (2) critical issues in tumor hormone receptor testing, (3) compelling data demonstrating that hormone receptor-positive breast cancer is a chronic disease, (4) data supportive of combined hormonal therapy with tamoxifen as the standard of care, and the limited justifications for awaiting the SOFT and TEXT trial results, (5) pharmacogenetic hypotheses with tamoxifen, (6) ethical issues in ovarian suppression vs ablative treatment, and (7) emerging data about the importance of primary tumor removal surgery itself and "surgical stress" in solid tumor management. PMID:20464842

  7. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

    NASA Astrophysics Data System (ADS)

    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.

  8. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  9. The association of fractional CO2 laser 10.600nm and photodynamic therapy in the treatment of onychomycosis*

    PubMed Central

    de Oliveira, Guilherme Bueno; Antonio, João Roberto; Antonio, Carlos Roberto; Tomé, Fernanda Alves

    2015-01-01

    BACKGROUND Onychomycosis is a fungal infection of the nails caused in most cases by dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Despite numerous available antifungal drugs for therapy of this infection, the cure rate is low, with high rates of relapse after treatment and side effects. OBJECTIVES To present a new option for the treatment of onychomycosis, in search of a more effective and rapid method than conventional ones. METHODS Patients underwent two sessions of CO2 fractional laser 10.600nm associated with photodynamic therapy. Mycological and digital photography were performed before and after the treatment. RESULTS McNemar test with continuity correction and degrees of freedom = 1: for clinical cure rate, 13.06, with p=0.00005; for mycological cure, 17.05, with p=0.00005; 72% felt fully satisfied with the procedure. CONCLUSIONS The use of fractional CO2 laser 10.600nm associated with photodynamic therapy can be effective in the treatment of onychomycosis, decreasing the risk of systemic lesions that may be triggered with prolonged use of oral antifungals. PMID:26375214

  10. Upconverting crystal/dextran-g-DOPE with high fluorescence stability for simultaneous photodynamic therapy and cell imaging.

    PubMed

    Wang, HanJie; Wang, Sheng; Liu, Zhongyun; Dong, Chunhong; Yang, Jiumin; Gong, Xiaoqun; Chang, Jin

    2014-04-18

    To date, the application of photodynamic therapy in deep tissue has been severely restricted by the limited penetration depth of excitation light, such as UV light and visible light. In this work, a protocol of upconverting crystal/dextran-g-DOPE nanocomplex (UCN/dextran-g-DOPE) was developed. The nanocomplex was assembled from the hydrophobic upconverting nanoparticle (UCN) core and hydrophilic lipid shell. The photosensitizer zinc phthalocyanine (ZnPc) loaded UCN/dextran-g-DOPE offers possibilities to overcome the problem mentioned above. The UCN core works as a transducer to convert deeply penetrating near-infrared light to visible light to activate ZnPc for photodynamic therapy. The dextran-g-DOPE lipid shell is used for loading ZnPc and protecting the whole system from nonspecific absorbance or corrosion during the transportation. The experiment results show that the nanocomplex is an individual sphere with an average size of 30 nm. The ZnPc was activated to produce singlet oxygen successfully by the upconverting fluorescence emitted from UCN. The nanocomplex has high fluorescence stability in alkaline or neutral buffer solutions. Importantly, the ZnPc loaded UCN/dextran-g-DOPE nanocomplex showed a significant inhibitory effect on tumor cells after NIR exposure. Our data suggest that a ZnPc loaded UCN/dextran-g-DOPE nanocomplex may be a useful nanoplatform for future PDT treatment in deep-cancer therapy based on the upconverting mechanism. PMID:24651122

  11. Application of Titanium Dioxide (TiO2) Nanoparticles in Photodynamic Therapy (PDT) of an Experimental Tumor

    NASA Astrophysics Data System (ADS)

    Miyoshi, Norio; Kume, Kyo; Tsutumi, Kotaro; Fukunaga, Yukihiro; Ito, Shinnji; Imamura, Yoshiaki; Bibin, Andriana B.

    2011-12-01

    Nano-sized particles has been used for the photodynamic and sonodynamic treatments of pre-clinical cancer study in previous studies [1-7]. In this study, the 5-aminolevulinic acid (5-ALA) solution mixed with TiO2 nanoparticles was oral-administrated into the nude mouse transplanted under the skin with a human prostate cancer cell line. The experimental tumor model tissue (7×7×7 mm3) was measured of the size at different times after the photodynamic therapy (PDT) by laser to take a growth curve of the tumor. The treatment efficacy was jugged from the growth curves comparing different conditions. In the presence of the nanoparticle, the PDT treatment effect was enhanced those in the absence of the particles. Furthermore, the sonodynamic therapy (SDT) effect also enhanced with the nanoparticle to produce more OH radicals by ultrasound irradiation. These combination therapy of PDT and SDT with nanoparticles was very effectively resulted to be useful as a clinical use in future.

  12. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    SciTech Connect

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-08-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

  13. Development of a new illumination procedure for photodynamic therapy of the abdominal cavity

    NASA Astrophysics Data System (ADS)

    Guyon, Laurie; Claude Lesage, Jean; Betrouni, Nacim; Mordon, Serge

    2012-03-01

    A homogeneous illumination of intra-abdominal organs is essential for successful photodynamic therapy of the abdominal cavity. Considering the current lack of outstanding light-delivery systems, a new illumination procedure was assessed. A rat model of peritoneal carcinomatosis was used. Four hours after intraperitoneal injection of hexaminolevulinate, a square illuminating panel connected to a 635-nm laser source was inserted vertically into the abdominal cavity. The abdominal incision was sutured and a pneumoperitoneum created prior to illumination. Light dosimetry was based on the calculation of the peritoneal surface by MRI. The rats were treated with a light dose of 20, 10, 5 or 2.5 J/cm2 administered continuously with an irradiance of 7 mW/cm2. The homogeneity of the cavity illumination was assessed by quantification of the photobleaching of the tumor lesions according to their localization and by scoring of that of the liver and of the bowel immediately after treatment. Photobleaching quantification for tumor lesions relied on the calculation of the fluorescence intensity ratio (after/before treatment) after recording of the lesions during blue-light laparoscopy and determination of their fluorescence intensity with Sigmascan Pro software. The procedure led to a homogeneous treatment of the abdominal cavity. No statistical difference was observed for the photobleaching values according to the localization of the lesions on the peritoneum (p=0.59) and photobleaching of the liver and of the intestine was homogeneous. We conclude that this procedure can successfully treat the major sites involved in peritoneal carcinomatosis.

  14. In vitro studies of the efficiency of two-photon activation of photodynamic therapy agents

    NASA Astrophysics Data System (ADS)

    Khurana, Mamta; Karotki, Aliaksandr; Collins, Hazel; Anderson, Harry L.; Wilson, Brian C.

    2006-09-01

    Age related macular degeneration (AMD) is a major cause of severe vision loss in the older population, due to ingrowth of new leaky blood vessels (neovasculature) from the choriocapillaris, which results in destruction of photoreceptors in the fovea and loss of central vision. "Standard" one-photon (1-?) photodynamic therapy (PDT) using Visudyne (R) is an approved method of AMD treatment but has the potential to damage healthy tissues lying above and below the neovasculature due to photosensitizer accumulation and its wide-beam 1-? excitation. Highly-targeted two-photon (2-?) excitation may avoid this, since, due to its non-linear intensity dependence, the probability of 2-? excitation is greatest in the focal plane, which intrinsically avoids out-of-focus damage to healthy tissues. The aim of the present study is to evaluate the 2-? efficiency of Visudyne and to compare it to the archetypal photosensitizer Photofrin (R). Since neovascular endothelium is targeted in AMD, an endothelial cell line (YPEN-1) was selected as the in vitro model. 2-? PDT was delivered using tightly focused ~300 fs laser pulses from a Ti:sapphire laser operating at 850 nm with 90 MHz pulse repetition rate. An assay was developed for quantification of the cellular damage using the permeability stain Hoechst 33258 and the viability stain SYTOX. Visudyne (LD 50= dose to kill 50% of cells: 500 J/cm2, 10 M, 7.2 ?g/ml) was about an order of magnitude more effective than Photofrin (LD50 : 7500 J/cm2, ~42 ?M, 25 ?g/ml). We also demonstrate for the first time the quadratic dependence of the cellular response to 2-? PDT. This in vitro work will lead to the design of optimized in vivo studies in animal models of AMD.

  15. Pathologic observation of two kinds of tumors in mice after photodynamic therapy with sulfonated aluminum phthalocyanine

    NASA Astrophysics Data System (ADS)

    Yu, Hong-Yu; Dong, Rong-Chun; Min, Hong-Bo; Chen, Ji-Yao; Cai, Huai-Xin

    1993-03-01

    Pathologic changes were observed in S180 fibrosarcoma transplanted in white mice of Kunming line and in human hepatocellular carcinoma transplanted in balb/c nu/nu nude mice after photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPC). The experimental tumors in mice were chosen with diameters in the range of 0.5 - 0.8 cm. A dose of 10 mg/kg AlSPC was given (iv). The dose of light (600 - 750 nm) was 180 J/cm2. Degeneration of tumor cells, microvascular hyperemia, stroma edema, and hemorrhage were found soon after PDT under the microscope and the hyperemia and hemorrhage in hepatocellular carcinoma seems more obvious than in S180 sarcoma. Heave hyperemia and hemorrhage can not always be seen in the degenerative and necrotic area in S180 sarcoma. With transmission electron microscopic technique, the most significant early changes are apparent degeneration of the mitochondria, slight dilation of rough endoplasmic reticula, a little increase of lysosmes (both in tumor cells and in endathelia), collagen fiber degeneration in the subendothelial zone of the capillary wall and in other connective collagen fibers, and slight edema in intercellular space and in the interstitial tissue surrounding capillaries immediately after completion of 30 min PDT. Additionally, the results were discussed in combination with our other study of histochemistry on seven kinds of tissue enzymes in hepatocellular carcinoma which shows the activities of these enzymes reduced to be inconsiderable from within 30 min to within 6 h after AlSPC-PDT, in which the activity of SDHase reduced most quickly. The pathologic study suggested the cellular membrane system, especially the mitochondria, was probably one of the main reaction targets of AlSPC-PDT though what is the most important primary target (the tumor cell's and endothelium's mitochondria or subendothelial zone, or some other structure) further study is required to answer.

  16. Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions

    SciTech Connect

    Tirand, Loraine; Bastogne, Thierry; Bechet, Denise M.Sc.; Linder, Michel; Thomas, Noemie; Frochot, Celine; Guillemin, Francois; Barberi-Heyob, Muriel

    2009-09-01

    Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm{sup 2}; fluence rate, 85 mW/cm{sup 2}). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent. Conclusions: Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.

  17. Antimicrobial photodynamic therapy for the decolonization of methicillin-resistant Staphylococcus aureus from the anterior nares

    NASA Astrophysics Data System (ADS)

    Street, Cale N.; Pedigo, Lisa; Gibbs, Aaron; Loebel, Nicolas G.

    2009-06-01

    The nosocomial infection rate has increased dramatically due to emergence of antibiotic resistant bacterial strains such as methicillin resistant Staphylococcus aureus (MRSA). The primary anatomical site of MRSA colonization is the anterior nares, and this reservoir represents a primary vector of transmission from non-infected carriers to susceptible individuals. Antimicrobial photodynamic therapy (aPDT) has been used successfully for topical disinfection in the oral cavity. The aim of this study was to evaluate the utility of aPDT for nasal MRSA decolonization at the preclinical and clinical level. The nasal aPDT system consists of a 670 nm diode laser fibre-optically coupled to a disposable light diffusing tip, used to activate a methylene blue based photosensitizer formulation. Preclinical testing was done both in a custom nasal reservoir model and on human skin cultures colonized on the epithelial surface with MRSA. Human clinical testing was performed by clinicians in regions in which the system is approved by the regulatory authority. In vitro testing demonstrated that aPDT eradicated planktonic MRSA in an energy and photosensitizer concentration dependent manner. Furthermore, aPDT eliminated sustained colonization of MRSA on cultured human epithelial surfaces, an effect that was sustained over multiple days post-treatment. In preliminary human testing, aPDT eradicated MRSA completely from the nose with total treatment times <10 minutes. aPDT is effective against MRSA when used topically in the nose. Energy dose and photosensitizer parameters have been optimized for the nasal environment. Controlled clinical studies are currently underway to further evaluate safety and efficacy.

  18. Reflectance Spectrophotometric Investigation Of Tissue Response In Photodynamic Therapy Of Cancer

    NASA Astrophysics Data System (ADS)

    Feather, J. W.; Driver, I.; Leslie, G.; Hajizadeh-Saffar, M.; Gilson, D.; King, P. R.; Dixon, B.

    1988-06-01

    Reflectance spectrophotometry has been used to investigate tumour and normal tissue responses to porphyrin mediated photodynamic therapy of cancer. Subcutaneously implanted isogenic fibrosarcomas were treated when they had grown to 10-12mm diameter. An Argon-ion pumped tunable dye laser provided 630nm cw light, which was delivered to the tumours either interstitially through a 200?m cleaved end fibre inserted into the centre of the tumour or transcutaneously through a 600?m cleaved end fibre mounted at distance from the overlying skin surface. A reflectance spectrophotometer employing fibre optic bundles to deliver light to and collect from the tissue was used to measure reflectance spectra (450-700nm) pre- and post-treatment in tumour and adjacent normal tissue of animals with and without photosensitiser. The reflectance data were converted to a parameter LIR (Logarithm of the Inverse Reflectance) whichmay be shown to be proportional to absorbance and therefore to tissue pigment concentration. Indices of total tissue haemoglobin and oxygen saturation levels have been derived based upon the differences in the shape of the LIR spectra of oxygenated and deoxygenated haemoglobin between 500 and 600nm. These indices provided information on the vascular state of tumours before treatment and the changes that occurred during and immediately after treatment. Preliminary results indicate a large decrease in tumour blood oxygenation during treatment with little recovery, at the dose level used, up to 2 hours post treatment in photosensitised animals, suggesting a decrease in tumour blood flow. After an immediate reduction in the haemoglobin index at the start of illumination, haemoglobin levels progressively rose throughout the treatment period and up to 2 hours post treatment. No significant changes occurred in non-photosensitised animals.

  19. Determination of threshold dose with d