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Sample records for one-time reduced-fluence photodynamic

  1. Photodynamic therapy for cancer

    MedlinePlus

    ... Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  2. Photodynamic therapy for cancer

    MedlinePlus

    ... Photoradiation therapy; Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  3. Photodynamic Therapy

    PubMed Central

    Dougherty, Thomas J.; Gomer, Charles J.; Henderson, Barbara W.; Jori, Giulio; Kessel, David; Korbelik, Mladen; Moan, Johan; Peng, Qian

    2015-01-01

    Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin®) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered. PMID:9637138

  4. 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

  5. Miniature, Lightweight, One-Time-Opening Valve

    NASA Technical Reports Server (NTRS)

    Jones, Jack; Wu, Juinn Jenq; Leland, Robert

    2008-01-01

    The figure depicts the main parts of a prototype miniature, lightweight, onetime- opening valve. Like some other miniature one-time-opening valves reported in previous issues of NASA Tech Briefs, this valve is opened by melting a material that blocks the flow path. This valve is designed to remain closed at some temperature between room temperature and cryogenic temperature until the time of opening. The prototype valve includes a 1/8-in. (3-mm) aluminum tube, one end of which is plugged with a solder comprising about 37 weight percent of lead and 63 weight percent of tin. The tube and the solder both have a coefficient of thermal expansion of 23 micron/m-K at room temperature. Before plugging, the interior surface of the plug end of the tube is cleaned with a commercial flux paste developed specifically for preparing aluminum for bonding with lead/tin solder. The solder is then melted into the cleaned end of the tube, forming the plug. In a test, the plugged tube was pressurized to 1,000 psi (6.9 MPa) with helium and leak-tested. It was then cooled to a temperature of 77 K (about 196 C) and again leak-tested at the same pressure. Finally, at a lower pressure, the plugged end of the tube was heated to about 200 C (the melting temperature of the solder is 183 C), causing the solder plug to be ejected (see figure). It has been estimated that in a subsequent version of the valve, the plug could be melted by electrical heating, using a nichrome wire having a mass of only 10 g.

  6. 48 CFR 225.7003-4 - One-time waiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false One-time waiver. 225.7003-4 Section 225.7003-4 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Other Statutory Restrictions on Foreign Acquisition 225.7003-4 One-time waiver. DoD may accept...

  7. One-Time Pad as a nonlinear dynamical system

    NASA Astrophysics Data System (ADS)

    Nagaraj, Nithin

    2012-11-01

    The One-Time Pad (OTP) is the only known unbreakable cipher, proved mathematically by Shannon in 1949. In spite of several practical drawbacks of using the OTP, it continues to be used in quantum cryptography, DNA cryptography and even in classical cryptography when the highest form of security is desired (other popular algorithms like RSA, ECC, AES are not even proven to be computationally secure). In this work, we prove that the OTP encryption and decryption is equivalent to finding the initial condition on a pair of binary maps (Bernoulli shift). The binary map belongs to a family of 1D nonlinear chaotic and ergodic dynamical systems known as Generalized Luröth Series (GLS). Having established these interesting connections, we construct other perfect secrecy systems on the GLS that are equivalent to the One-Time Pad, generalizing for larger alphabets. We further show that OTP encryption is related to Randomized Arithmetic Coding - a scheme for joint compression and encryption.

  8. Photodynamic therapy in dentistry.

    PubMed

    Konopka, K; Goslinski, T

    2007-08-01

    Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemotherapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections. Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination. PMID:17652195

  9. Photodynamic immune modulation (PIM)

    NASA Astrophysics Data System (ADS)

    North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

    1999-09-01

    Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

  10. Secure direct communication with a quantum one-time pad

    SciTech Connect

    Deng Fuguo; Long Guilu

    2004-05-01

    Quantum secure direct communication is the direct communication of secret messages without first producing a shared secret key. It may be used in some urgent circumstances. Here we propose a quantum secure direct communication protocol using single photons. The protocol uses batches of single photons prepared randomly in one of four different states. These single photons serve as a one-time pad which is used directly to encode the secret messages in one communication process. We also show that it is unconditionally secure. The protocol is feasible with present-day technique.

  11. Physical key-protected one-time pad

    NASA Astrophysics Data System (ADS)

    Horstmeyer, Roarke; Judkewitz, Benjamin; Vellekoop, Ivo M.; Assawaworrarit, Sid; Yang, Changhuei

    2013-12-01

    We describe an encrypted communication principle that forms a secure link between two parties without electronically saving either of their keys. Instead, random cryptographic bits are kept safe within the unique mesoscopic randomness of two volumetric scattering materials. We demonstrate how a shared set of patterned optical probes can generate 10 gigabits of statistically verified randomness between a pair of unique 2 mm3 scattering objects. This shared randomness is used to facilitate information-theoretically secure communication following a modified one-time pad protocol. Benefits of volumetric physical storage over electronic memory include the inability to probe, duplicate or selectively reset any bits without fundamentally altering the entire key space. Our ability to securely couple the randomness contained within two unique physical objects can extend to strengthen hardware required by a variety of cryptographic protocols, which is currently a critically weak link in the security pipeline of our increasingly mobile communication culture.

  12. Physical key-protected one-time pad.

    PubMed

    Horstmeyer, Roarke; Judkewitz, Benjamin; Vellekoop, Ivo M; Assawaworrarit, Sid; Yang, Changhuei

    2013-01-01

    We describe an encrypted communication principle that forms a secure link between two parties without electronically saving either of their keys. Instead, random cryptographic bits are kept safe within the unique mesoscopic randomness of two volumetric scattering materials. We demonstrate how a shared set of patterned optical probes can generate 10 gigabits of statistically verified randomness between a pair of unique 2 mm(3) scattering objects. This shared randomness is used to facilitate information-theoretically secure communication following a modified one-time pad protocol. Benefits of volumetric physical storage over electronic memory include the inability to probe, duplicate or selectively reset any bits without fundamentally altering the entire key space. Our ability to securely couple the randomness contained within two unique physical objects can extend to strengthen hardware required by a variety of cryptographic protocols, which is currently a critically weak link in the security pipeline of our increasingly mobile communication culture. PMID:24345925

  13. Physical key-protected one-time pad

    PubMed Central

    Horstmeyer, Roarke; Judkewitz, Benjamin; Vellekoop, Ivo M.; Assawaworrarit, Sid; Yang, Changhuei

    2013-01-01

    We describe an encrypted communication principle that forms a secure link between two parties without electronically saving either of their keys. Instead, random cryptographic bits are kept safe within the unique mesoscopic randomness of two volumetric scattering materials. We demonstrate how a shared set of patterned optical probes can generate 10 gigabits of statistically verified randomness between a pair of unique 2 mm3 scattering objects. This shared randomness is used to facilitate information-theoretically secure communication following a modified one-time pad protocol. Benefits of volumetric physical storage over electronic memory include the inability to probe, duplicate or selectively reset any bits without fundamentally altering the entire key space. Our ability to securely couple the randomness contained within two unique physical objects can extend to strengthen hardware required by a variety of cryptographic protocols, which is currently a critically weak link in the security pipeline of our increasingly mobile communication culture. PMID:24345925

  14. Photodynamic Therapy (PDT): PDT Mechanisms

    PubMed Central

    Allison, Ron R.

    2013-01-01

    Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients. PMID:23422955

  15. [Photodynamic modulation of cellular functions].

    PubMed

    Li, Yuan; Jiang, Hong-Ning; Cui, Zong-Jie

    2016-08-25

    Photodynamic action, due to the rather limited lifetime (1 μs) and effective reactive distance of singlet oxygen (< 10 nm), could subcellular-specifically regulate different cellular functions. Photodynamic action could activate permanently cholecystokinin (CCK) 1 receptors, and sensitize or desensitize other G protein-coupled receptors. The emergence in recent years of genetically- encoded protein photosensitisers has enabled more precisely-targeted photodynamic modulation of subcellular organelles and functional proteins. Protein photosensitisers (such as KillerRed, miniSOG or SOPP) expressed on the plasma membrane, mitochondria, lysosomes or endoplasmic reticulum can modulate photodynamically subcellular functions and fine-tune protein activity by targeted photooxidation. With the newly emerged active illumination technique, simultaneous photodynamic action localized at multiple sites is now possible, and the contribution of subcellular regions to the whole cell or individual cells to a cell cluster could be quantitated. Photodynamic action with protein photosensitiser will be a powerful tool for nano-manipulation in cell physiology research. PMID:27546513

  16. Photodynamic Therapy Of Cancer

    NASA Astrophysics Data System (ADS)

    Dougherty, Thomas J.

    1989-03-01

    Photodynamic therapy (PDT) has been used experimentally in cancer patients since 1976, with an estimated 3,000-4,000 patients treated world-wide, most since 1982. Phase III, comparative randomized clinical trials are under way for regulatory approval of Photofrin II, a purified version of hematoporphyrin derivative (Hpd). Several recent advances in both the clinical application of PDT and basic understanding of mechanisms are noteworthy. For example, it is now recognized that the photosensitizer undergoes photobleaching during treatment which may provide a therapeutic advantage in treatment. Clinical trials using lower drug doses seem to be consistent with this expectation. Advances in light delivery systems and dosimetry have also been achieved. It is now clear that in at least some experimental animal tumors, destruction of the vasculature system in both the tumor and surrounding normal tissue is necessary for 'cure', a process which may involve release of inflammatory and other factors. It is unclear if this is relevant to humans. Because of the problem of cutaneous photosensitivity and other factors, a search for other photo-sensitizers is being carried out by several groups, with early encouraging results being reported for certain phthalocyanines, purpurins and others.

  17. 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.

  18. Photodynamic therapy--aspects of pain management.

    PubMed

    Fink, Christine; Enk, Alexander; Gholam, Patrick

    2015-01-01

    Topical photodynamic therapy (PDT) is a highly effective and safe treatment method for actinic keratoses with an excellent cosmetic outcome and is commonly used for the therapy of large areas of photodamaged skin with multiple clinically manifest and subclinical lesions. However, the major drawback of photodynamic therapy is the pain experienced during the treatment that can be intense and sometimes even intolerable for patients, requiring interruption or termination of the process. Several strategies for controlling pain during photodynamic therapy have been studied but few effective methods are currently available. Therefore, this review puts the spotlight on predictors on pain intensity and aspects of pain management during photodynamic therapy. PMID:25640485

  19. 24 CFR 203.280 - One-time or Up-front MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false One-time or Up-front MIP. 203.280... SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Mortgage Insurance Premiums-One-Time Payment § 203.280 One-time or Up-front MIP. For mortgages for which a one-time or up-front MIP is to...

  20. Photodynamic Diagnosis and Therapy of Cancer

    SciTech Connect

    Subiel, Anna

    2010-01-05

    This paper gives brief information about photodynamic method used in diagnosis and therapy for cancer and other human body disorders. In particular it concentrates on detection and analysis of fluorescent dye, i.e. protoporphyrin IX (PpIX) and its two-photon excitation (TPE) process, which offers photodynamic method many fascinating possibilities.

  1. 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.

  2. 24 CFR 203.281 - Calculation of one-time MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Calculation of one-time MIP. 203... AUTHORITIES SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Mortgage Insurance Premiums-One-Time Payment § 203.281 Calculation of one-time MIP. (a) The applicable premium percentage...

  3. 24 CFR 888.320 - One-time Contract Rent determination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false One-time Contract Rent... Elderly or Handicapped, and Special Allocations Projects § 888.320 One-time Contract Rent determination..., as described in § 888.301(c), may request a one-time Contract Rent determination, to be effective...

  4. 24 CFR 203.283 - Refund of one-time MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Refund of one-time MIP. 203.283... SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Mortgage Insurance Premiums-One-Time Payment § 203.283 Refund of one-time MIP. (a) The Commissioner shall provide for the refund to...

  5. Photodynamic antimicrobial activity of hypocrellin A.

    PubMed

    Su, Yujie; Sun, Jun; Rao, Shengqi; Cai, Yujie; Yang, Yanjun

    2011-04-01

    Antimicrobial photodynamic therapy is a recently developed therapeutic option that combines a non-toxic photosensitizer with harmless visible light to damage the microbial cell. Hypocrellin A (HA), a natural occurring lipid-soluble perylenequinone pigment, has gained considerable interest since its anticancer and antiviral activities have been reported. Here, we examined the antimicrobial activity of HA against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Salmonella typhimurium). The results indicate that HA has a photodynamic antimicrobial activity against both Gram-positive and Gram-negative bacteria when CaCl(2) or MgCl(2) was employed. A loose binding has been established between HA and the organisms. Molecular oxygen is significantly involved in the photodynamic action of HA. Furthermore, HA maintains a photodynamic activity in terms of both types I and II reactions. Our results confirm the potential of HA to be used as a photosensitizer in antimicrobial photodynamic therapy. PMID:21300554

  6. Temperature effects in photodynamic processes

    NASA Astrophysics Data System (ADS)

    Hovhannisyan, Vladimir A.; Avetisyan, Hasmik A.; Mathevosyan, Margarita B.; Elbakyan, Egishe G.

    2005-04-01

    Photodynamic activity of several dyes on Drosophila melanogaster at different temperatures (15-35°C) inside of test-tubes was investigated. Both phototoxic sensitizers (chlorin e6, methylene blue, etc. -group A) and non active compounds (hemoglobin, brilliant green, pyronine, etc.-group B) were used. Dyes of 10-5-10-3 M concentration were added to the food for drosophila 24 hours before irradiation. Solar radiation, narrow-band halogen lamps, LEDs and laser were used as a photo-stimulator. Irradiation parameters: I <= 45mW/cm2 and 0.2photodynamic effect. This, probably, is concerned with the toxic photoproduct suppression by the inactive dye. Experimental model of drosophila allows to investigate photosensitization impact within wide temperature range, to find out the processes, when using combination of dyes, as well as to study photodynamic effect on reproductive functions of insects.

  7. Photodynamic treatment for surface sanitation

    NASA Astrophysics Data System (ADS)

    Brovko, Lubov; Romanova, Nadya A.; Leslie, Christina; Ollivier, Helene; Griffiths, Mansel W.

    2005-09-01

    The bactericidal effect of visible light illumination on bacteria treated with non-toxic photosensitizers (PS) has been shown previously, its effectiveness depended on both cell type and nature of photosensitizer used. The photosensitizer (PS)-mediated bactericidal effect of light against different types of microorganisms including vegetative bacteria (both in planktonic form and in biofilms), bacterial spores, yeasts, viruses was investigated for both cells in liquid media, and on surface. Bactericidal effect was monitored for different photosensitizer such as TBO and derivatives of rosamine at different concentrations. The possibility of using photodynamic treatment for surface sanitation was investigated.

  8. A history of photodynamic therapy.

    PubMed

    Daniell, M D; Hill, J S

    1991-05-01

    The origins of light as a therapy in medicine and surgery are traced from antiquity to the modern day. Phototherapy began in ancient Greece, Egypt and India but disappeared for many centuries, only being rediscovered by Western civilization at the beginning of the twentieth century through the Dane, Niels Finsen, and the Germans Oscar Raab and Herman von Tappeiner. The discovery of the tumour-localizing ability of haematoporphyrin, together with its phototoxic effect on tumour cells led to the development of photodynamic therapy, a promising tool in modern cancer treatment. PMID:2025186

  9. Photodynamic therapy: present and future

    NASA Astrophysics Data System (ADS)

    Waidelich, Raphaela M.

    2000-06-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and its subsequent activation by light of the appropriate wavelength, resulting in destruction of cells containing the agent. PDT has been designed as a promising new modality in the treatment of various malignant and nonmalignant disease since the early 1980s. Recent chemical and physical developments have brought forth new methods of PDT. We provide an overview of photosensitizers, photobiology and photochemistry, and light sources available for PDT. Clinical and preclinical PDT studies are discussed.

  10. 24 CFR 203.280 - One-time or Up-front MIP.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false One-time or Up-front MIP. 203.280... Payment § 203.280 One-time or Up-front MIP. For mortgages for which a one-time or up-front MIP is to be... the mortgage by the Commissioner or the up-front portion of the total obligation, as...

  11. 24 CFR 203.280 - One-time or Up-front MIP.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false One-time or Up-front MIP. 203.280... Payment § 203.280 One-time or Up-front MIP. For mortgages for which a one-time or up-front MIP is to be... the mortgage by the Commissioner or the up-front portion of the total obligation, as...

  12. 24 CFR 203.280 - One-time or Up-front MIP.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false One-time or Up-front MIP. 203.280... Payment § 203.280 One-time or Up-front MIP. For mortgages for which a one-time or up-front MIP is to be... the mortgage by the Commissioner or the up-front portion of the total obligation, as...

  13. 24 CFR 203.280 - One-time or Up-front MIP.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false One-time or Up-front MIP. 203.280... Payment § 203.280 One-time or Up-front MIP. For mortgages for which a one-time or up-front MIP is to be... the mortgage by the Commissioner or the up-front portion of the total obligation, as...

  14. Photosensitizers for photodynamic immune modulation

    NASA Astrophysics Data System (ADS)

    North, John R.; Boch, Ronald; Hunt, David W. C.; Ratkay, Leslie G.; Simkin, Guillermo O.; Tao, Jing-Song; Richter, Anna M.; Levy, Julia G.

    2000-06-01

    PDT may be an effective treatment for certain immune-mediated disorders. The immunomodulatory action of PDT is likely a consequence of effects exerted at a number of levels including stimulation of specific cell signaling pathways, selective depletion of activated immune cells, alteration of receptor expression by immune and non-immune cells, and the modulation of cytokine availability. QLT0074, a potent photosensitizer that exhibits rapid clearance kinetics in vivo, is in development for the treatment of immune disorders. In comparison to the well-characterized and structurally related photosensitizer verteporfin, lower concentrations of QLT0074 were required to induce apoptosis in human blood T cells and keratinocytes using blue light for photoactivation. Both photosensitizers triggered the stress activated protein kinase (SAPK) and p38 (HOG1) pathways but not extracellularly regulated kinase (ERK) activity in mouse Pam212 keratinocytes. In cell signaling responses, QLT0074 was active at lower concentrations than verteporfin. For all in vitro test systems, the stronger photodynamic activity of QLT0074 was associated with a greater cell uptake of this photosensitize than verteporfin. In mouse immune models, sub-erythemogenic doses of QLT0074 in combination with whole body blue light irradiation inhibited the contact hypersensitivity response and limited the development of adjuvant-induced arthritis. QLT0074 exhibits activities that indicate it may be a favorable agent for the photodynamic treatment of human immune disease.

  15. Vascular effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fyodorov, Svyatoslav N.; Kopayeva, V. G.; Andreev, J. B.; Ponomarev, Gelii V.; Stranadko, Eugeny P.; Suchin, H. M.

    1996-01-01

    Vascular effect of PDT has been studied in patients with corneal vascularized leucomas (10 patients) and in patients with corneal neovascularized transplant (3 patients). For vascularized leucomas the method of photodynamic therapy consisted of the local injection of dimegin (deiteroporphyrin derivative) into the space of the newly-formed vessels under operating microscope (opton) with the microneedle (diameter 200 microns) and corneal irradiation by the operating microscope light. For corneal neovascularized transplant the injection of photogem (hematoporphyrin derivative) intravenously were made with subsequent irradiation by light of dye laser (5 hours after the injection) with light density of 150 mW/cm2 for 15 minutes. In all the cases at the time of irradiation the aggregated blood flow was appeared, followed by blood flow stasis. In postoperative period the vessels disintegrated into separate fragments which disappeared completely after 10 - 15 days. Taking into account the data of light microscopy, the disappearance of the vessels took place as a result of the vascular endothelium lisis along the vascular walls. Neovascularized cornea and newly-formed vessels in tumor stroms have much in common. The vessel alterations study presented in this paper, may serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.

  16. 75 FR 22804 - Submission for OMB Review; American Recovery and Reinvestment Act-One-Time Reporting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    .... SUPPLEMENTARY INFORMATION: A. Background The Notice, published in the Federal Register at 75 FR 18835, on April...; American Recovery and Reinvestment Act--One-Time Reporting, Compensation Requirements AGENCIES: Department... Recovery and Reinvestment Act--One-time Reporting, Compensation Requirements published in the...

  17. 75 FR 18835 - Submission for OMB Review; American Recovery and Reinvestment Act-One-Time Reporting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... requirement concerning the one-time reporting, compensation requirements. A request for public comments was published in the Federal Register at 74 FR 14639, on March 31, 2009. Public comments are particularly...; American Recovery and Reinvestment Act--One-Time Reporting, Compensation Requirements AGENCY: Department...

  18. 24 CFR 888.420 - One-time Contract Rent determination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false One-time Contract Rent... Projects § 888.420 One-time Contract Rent determination. (a) Determining the amount of the new Contract Rent. Project owners eligible for retroactive payments, as described in § 888.401(c), may request a...

  19. 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.

  20. Photodynamic therapy of malignancy of skin with He-Ne laser

    NASA Astrophysics Data System (ADS)

    Zhu, Jing; Shi, Hongmin; Zhang, Hui-Guo

    2005-07-01

    Objective: Research on the photodynamic therapy of malignancy of skin with He-Ne Laser. Methods: 35 cases of skin malignancy were treated with photodynamic therapy. He-Ne laser with output power of 600 mW was used and hematoporphyrin derivative (HPD) was applied, at a dose of 5mg/kg of body. 15 patients received simple surface irradiation, 20 patients received both surface and insertion irradiation. 28 patients underwent treatment for one time, 7 patients twice. The 12 cases were basel cell carcinoma, 7 cases were squamous cell carcinoma, 4 cases were skin carcinoma in situ, 8 cases were skin Paget's disease, 1 case was Paget's disease accompanying adenoid carcinoma, 1 case malignant melanoma, 1 case red hypertrophic disease, 1 case recurrent perianal carcinoma deriving from rectum.

  1. 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

  2. [Photodynamic Therapy for Lung Cancer].

    PubMed

    Ohtani, Keishi; Ikeda, Norihiko

    2016-07-01

    In Japan, Photodynamic therapy (PDT) is recommended as a treatment option for centrally located early-stage lung cancers (CLELCs). It is a minimally invasive treatment with excellent anti-tumor effects. The 2nd generation photosensitizer, talaporfin sodium has strong anti-tumor effects with much less photosensitivity than porfimer sodium. Moreover, the laser equipment is compact and portable, and talaporfin sodium is now the current mainstay of PDT for lung cancer. For successful PDT, accurate evaluation of tumor extent and bronchial invasion is crucial. Detailed examination of the tumor using autofluorescence bronchoscopy and endobronchial ultrasonography or optical coherence tomography is extremely useful before PDT. At present, PDT has become the 1st choice of treatment for CLELC in institutions with the necessary equipment. It can also be effective for advanced lung cancer causing tracheobronchial obstruction. With such advances in PDT for CLELC, we are expanding the indications of PDT for not only CLELC, but also peripheral type lung cancer. PMID:27440036

  3. Antimicrobial photodynamic therapy: An overview

    PubMed Central

    Rajesh, S.; Koshi, Elizabeth; Philip, Koshi; Mohan, Aparna

    2011-01-01

    Inflammatory periodontal disease caused by dental plaque is characterized by the clinical signs of inflammation and loss of periodontal tissue support. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. But the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. The possibility of development of resistance to antibiotics by the target organism has led to the development of a new antimicrobial concept with fewer complications. Photodynamic therapy (PDT) involves the use of low power lasers with appropriate wavelength to kill micro organisms treated with a photosensitizer drug. PDT could be a useful adjunct to mechanical as well as antibiotics in eliminating periopathogenic bacteria. PMID:22368354

  4. BODIPY Dyes In Photodynamic Therapy

    PubMed Central

    Kamkaew, Anyanee; Lim, Siang Hui; Lee, Hong Boon; Kiew, Lik Voon; Chung, Lip Yong

    2012-01-01

    BODIPY dyes tends to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas. PMID:23014776

  5. 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 (λ=630 nm, Pmax=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (λ=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.

  6. Selective tumor destruction with photodynamic therapy: exploitation of photodynamic thresholds

    NASA Astrophysics Data System (ADS)

    Barr, Hugh

    1991-11-01

    The uptake and distribution of the photosensitizer aluminum sulphonated phthalocyanine (AlSPc) has been studied. In a variety of experimentally induced gastrointestinal tumors the photosensitizer is retained between 24 - 48 hours after intravenous administration compared with the adjacent normal tissue in which the tumor arose. However, the maximum tumor-to- normal-tissue ratio was only 2:1. Quantitative fluorescence photometry using digital image processing, with a CCD camera and helium neon laser, was used to probe the microscopic localization of the photosensitizer in tissue sections of tumor and normal tissue. Selective localization of the photosensitizer was nonspecific in tumor stroma and there was never any significant difference between normal and neoplastic cells. Exploitation of the small differences in photosensitizer concentration, photodynamic threshold effects, and photosensitizer photodegration allows up to 2 mm of selective tumor damage to be produced in a tumor, when a similar light dose will produce no damage in adjacent normal tissue. However, selective eradication of a tumor without adjacent tissue damage will not be possible by using these methods. This paper reviews this previously reported data.

  7. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    PubMed Central

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  8. 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

  9. Photodynamic therapy for skin cancer

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Julius, Clark E.; Hartman, Donald L.

    1996-04-01

    Photodynamic therapy was used to treat 111 lesions in 27 cases with squamous and basal cell carcinoma. There were 82 squamous cell carcinomas and 29 basal cell carcinomas. Photofrin was administered intravenously at either 1.0 mg/kg or 0.75 mg/kg. An argon/dye laser was used to deliver 630 nm light to the lesion superficially at either 215 J/cm2 or 240 J/cm2. In some cases the laser light was delivered both superficially and interstitially. The laser light was delivered two to four days after the Photofrin injection. There were 105 complete responses and 5 partial responses. One patient was lost to follow-up. Among partial responses were basal cell carcinoma on the tip of the nose and morphea basal cell carcinoma of the left cheek. Another partial response occurred in a basal cell carcinoma patient where insufficient margins were treated due to the proximity to the eye. When 0.75 mg/kg drug dose was used, the selectivity of tumor necrosis was improved. Decreased period of skin photosensitivity was documented in some cases.

  10. 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

  11. Photodynamic Therapy in Pediatric Dentistry

    PubMed Central

    da Silva Barbosa, Patricia; Duarte, Danilo Antônio; Leite, Mariana Ferreira; de Sant' Anna, Giselle Rodrigues

    2014-01-01

    Conservation of deciduous teeth with pulp alterations caused by caries and trauma is a major therapeutic challenge in pediatric dentistry as a result of the internal anatomy and life cycle characteristic. It is essential that the root canal procedures sanitizers have a performance in eliminating bacterial. In this context, antimicrobial photodynamic therapy (PAT) is promising and emerging as adjuvant therapy in an attempt to eliminate the microorganisms persistent to chemi-mechanical preparation. Since there is presence of oxygen in cells, photosensitizer activated by light can react with molecules in its vicinity by electrons' or hydrogen's transfer, leading to microorganism death. This paper reports the case of 4-year-old patient, female, with early childhood caries. The proposed endodontic treatment incuded chemomechanical treatment allied to PAT in the decontamination of root canals using methylene blue dye 50 μg/mL during 3–5 minutes and 40 J/cm2 as energy density, taking into account the need for tissue penetration and effectiveness of PAT inside the dentinal tubules. PMID:25371829

  12. Strategies for targeted antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Verma, Sarika; Sallum, Ulysses; Zheng, Xiang; Hasan, Tayyaba

    2009-06-01

    The photophysics and mechanisms of cell killing by photodynamic therapy (PDT) have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modality expands with regard to both anatomical sites and diseases, it is important to develop strategies for enhancing PDT outcomes. Our group has focused on developing targeting strategies to enhance PDT for both cancerous as well as anti-microbial applications. In this article, we will discuss photosensitizer modification and conjugation strategies for targeted antimicrobial photodynamic therapy.

  13. 24 CFR 203.283 - Refund of one-time MIP.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Refund of one-time MIP. 203.283 Section 203.283 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER...

  14. 24 CFR 203.283 - Refund of one-time MIP.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Refund of one-time MIP. 203.283 Section 203.283 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER...

  15. 77 FR 10799 - Revised Guidance for Requesting One-Time Movement (OTM) Approvals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Revised Guidance for Requesting One-Time Movement (OTM) Approvals AGENCY... Administrator for Railroad Safety/Chief Safety Officer. These approvals are generally referred to as...

  16. 77 FR 70876 - Revised Guidance for Requesting One-Time Movement Approvals (OTMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Revised Guidance for Requesting One-Time Movement Approvals (OTMA) AGENCY.... SUMMARY: FRA is notifying the public of the availability of revised guidance for requesting...

  17. 78 FR 54252 - Information Collection; American Recovery and Reinvestment Act-Reporting Requirements-One Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-03

    ... FR 58389, for the number of respondents required to comply with the requirements of FAR subpart 4.15... Register on September 24, 2010, at 75 FR 58389. No public comments were received in prior years that have...; American Recovery and Reinvestment Act-- Reporting Requirements--One Time Reporting Requirements for...

  18. Inside the Black Box: What Happens on a One-Time Field Trip?

    ERIC Educational Resources Information Center

    Kraybill, Anne

    2014-01-01

    Crystal Bridges Museum of American Art opened on November 11, 2011. Located in Bentonville, Arkansas, it was the first art museum of its size in the region. Since few students had ever been to a museum, this situation provided an opportunity to causally measure the impact of a one-time art museum field trip upon student outcomes through the…

  19. 24 CFR 888.320 - One-time Contract Rent determination.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false One-time Contract Rent determination. 888.320 Section 888.320 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT...

  20. 24 CFR 888.320 - One-time Contract Rent determination.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false One-time Contract Rent determination. 888.320 Section 888.320 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT (CONTINUED) OFFICE OF THE ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT...

  1. One-time tillage of no-till: Effects on nutrients, mycorrhizae, and phosphorus uptake

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stratification of nutrient availability, especially of P, that develops with continuous no-till (NT) can affect runoff nutrient concentration and possibly nutrient uptake. The effects of composted manure application and one-time tillage of NT on the distribution of soil chemical properties, root co...

  2. Photodynamic application in neurosurgery: present and future

    NASA Astrophysics Data System (ADS)

    Kostron, Herwig

    2009-06-01

    Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence guided tumor resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as adjunctive treatment for malignant brain tumours. This review provides an overview on the current clinical data and trials as well as on photosensitisers, technical developments and indications for photodynamic application in Neurosurgery. Furthermore new developments and clinical significance of FGR for neurosurgery will be discussed. Over 1000 patients were enrolled in various clinical phase I/II trials for PDT for malignant brain tumours. Despite various treatment protocols, variation of photosensitisers and light dose there is a clear trend towards prolonging median survival after one single PDT as compared to conventional therapeutic modalities. The median survival after PDT for primary glioblastoma multiforme WHO IV was 19 months and for recurrent GBM 9 months as compared to standard convential treatment which is 15 months and 3 months, respectively. FGR in combination with adjunctive radiation was significantly superior to standard surgical resection followed by radiation. The combination of FGR/PDD and intraoperative PDT increased significantly survival in recurrent glioblastoma patients. The combination of PDD/ FGR and PDT offers an exciting approach to the treatment of malignant brain tumours "to see and to treat." PDT was generally well tolerated and side effects consisted of occasionally increased intracranial pressure and prolonged skin sensitivity against direct sunlight. This review covers the current available data and draws the future potential of PDD and PDT for its application in neurosurgery.

  3. Adventures in photodynamic therapy: 1976-2008

    PubMed Central

    Kessel, David

    2010-01-01

    While the concept of photodynamic therapy dates from 1900, and there have been periodic re-discoveries, the clinical era really began with the studies by Dougherty and associates in the early 1970s. This report relates my encounter with the field of PDT, along with experimental approaches to the elucidation of pertinent phototoxic mechanisms. PMID:21037798

  4. Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug reactions.

    PubMed

    Alagoz, O; Durham, D; Kasirajan, K

    2016-04-01

    We evaluated the cost-effectiveness of one-time pharmacogenomic testing for preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed a Markov-based Monte Carlo microsimulation model to represent the ADR events in the lifetime of each patient. The base-case considered a 40-year-old patient. We measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and estimated costs using 2013 US$. In the base-case, one-time genetic testing had an incremental cost-effectiveness ratio (ICER) of $43 165 (95% confidence interval (CI) is ($42 769,$43 561)) per additional LY and $53 680 per additional QALY (95% CI is ($53 182,$54 179)), hence under the base-case one-time genetic testing is cost-effective. The ICER values were most sensitive to the average probability of death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and cost of genetic testing. PMID:25987241

  5. Design of True Random One-Time Pads in DNA XOR Cryptosystem

    NASA Astrophysics Data System (ADS)

    Hirabayashi, Miki; Kojima, Hiroaki; Oiwa, Kazuhiro

    We present a new model to realize true random one-time pad (OTP) encryption using DNA self-assembly. OTP is an unbreakable cryptosystem if the pad (random key) is truly random, never reused, and kept secret. Mathematical algorithms can generate pseudo-random numbers only. "True" random numbers can be generated from a physical process such as thermal noise. In this work, we propose a new tile-colony algorithm that can utilize the DNA hybridization process as an effective source for the random key construction, and discuss the error tolerance of this method. Our results indicate that the molecular computation using DNA motifs will provide promising OTP applications.

  6. Electrical probe characteristic recovery by measuring only one time-dependent parameter

    NASA Astrophysics Data System (ADS)

    Costin, C.; Popa, G.; Anita, V.

    2016-03-01

    Two straightforward methods for recovering the current-voltage characteristic of an electrical probe are proposed. Basically, they consist of replacing the usual power supply from the probe circuit with a capacitor which can be charged or discharged by the probe current drained from the plasma. The experiment requires the registration of only one time-dependent electrical parameter, either the probe current or the probe voltage. The corresponding time-dependence of the second parameter, the probe voltage, or the probe current, respectively, can be calculated using an integral or a differential relation and the current-voltage characteristic of the probe can be obtained.

  7. Electrical probe characteristic recovery by measuring only one time-dependent parameter.

    PubMed

    Costin, C; Popa, G; Anita, V

    2016-03-01

    Two straightforward methods for recovering the current-voltage characteristic of an electrical probe are proposed. Basically, they consist of replacing the usual power supply from the probe circuit with a capacitor which can be charged or discharged by the probe current drained from the plasma. The experiment requires the registration of only one time-dependent electrical parameter, either the probe current or the probe voltage. The corresponding time-dependence of the second parameter, the probe voltage, or the probe current, respectively, can be calculated using an integral or a differential relation and the current-voltage characteristic of the probe can be obtained. PMID:27036776

  8. Methodologies for estimating one-time hazardous waste generation for capacity generation for capacity assurance planning

    SciTech Connect

    Tonn, B.; Hwang, Ho-Ling; Elliot, S.; Peretz, J.; Bohm, R.; Hendrucko, B.

    1994-04-01

    This report contains descriptions of methodologies to be used to estimate the one-time generation of hazardous waste associated with five different types of remediation programs: Superfund sites, RCRA Corrective Actions, Federal Facilities, Underground Storage Tanks, and State and Private Programs. Estimates of the amount of hazardous wastes generated from these sources to be shipped off-site to commercial hazardous waste treatment and disposal facilities will be made on a state by state basis for the years 1993, 1999, and 2013. In most cases, estimates will be made for the intervening years, also.

  9. 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

  10. PIC Algorithm with Multiple Poisson Equation Solves During One Time Step

    NASA Astrophysics Data System (ADS)

    Ren, Junxue; Godar, Trenton; Menart, James; Mahalingam, Sudhakar; Choi, Yongjun; Loverich, John; Stoltz, Peter H.

    2015-09-01

    In order to reduce the overall computational time of a PIC (particle-in-cell) computer simulation, an attempt was made to utilize larger time step sizes by implementing multiple solutions of Poisson's equation within one time step. The hope was this would make the PIC simulation stable at larger time steps than an explicit technique can use, and using larger time steps would reduce the overall computational time, even though the computational time per time step would increase. A three-dimensional PIC code that tracks electrons and ions throughout a three-dimensional Cartesian computational domain is used to perform this study. The results of altering the number of times Poisson's equation is solved during a single time step are presented. Also, the size of the time that can be used and still maintain a stable solution is surveyed. The results indicate that using multiple Poisson solves during one time step provides some ability to use larger time steps in PIC simulations, but the increase in time step size is not significant and the overall simulation run time is not reduced

  11. 75 FR 10004 - Bureau of Educational and Cultural Affairs (ECA) Request for Grant Proposals (RFGP): One-time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    ... of Educational and Cultural Affairs (ECA) Request for Grant Proposals (RFGP): One-time Competitive Grants Program-- Competition B--Professional, Cultural, and Youth One-time Grants Program Announcement Type: New Grant. Funding Opportunity Number: ECA/PE/C-10-One-time-Comp. B. Catalog of Federal...

  12. Antitumor immune reaction elicited by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    1999-06-01

    This work examines why photodynamic therapy (PDT) is capable of eliciting a strong immune reaction against treated solid tumors. It is postulated that this phenomenon originates from the basic charter of the insult inflicted by the photodynamic treatment, which is dominated by singlet oxygen-mediated oxidative stress. The early event associated with this initial impact, which is of major relevance for the development of immune response, is the generation of photo-oxidative lesions responsible for the activation of cellular signal transduction pathways and consequent induction of stress proteins. Importantly, these lesions, as well as other types of PDT mediated oxidative injury, have a strong pro-inflammatory character. It is suggested that the antitumor immune response is primed and propagated by the PDT-induced inflammatory process. Of critical importance for the immune recognition of treated tumor is the generation of large amounts of cancer cell debris that occurs rapidly following PDT treatment.

  13. Heat-shock Proteins and Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Baylis, Joanne; Downs, Craig A.; Jones, Linda R.; Heckathorn, Scott A.

    1998-11-01

    Many cancer treatments, such as photodynamic therapy, generate active oxygen species, often in the mitochondria. These oxygen species adversely react with cellular processes, thereby destroying cancer cells and tissue. Heat-shock proteins are up-regulated in response to heat stress or other environmental stresses and are known to protect cells from active oxygen species. In tumor cells, heat-shock proteins accumulate in the mitochondria under non-stress conditions at higher levels than in normal cells. The objective of our work is to determine whether specific mitochondrial heat-shock proteins are responsible for the increased resistance of cancer cells to oxidative-based anti-cancer therapies. We will first determine which heat-shock proteins accumulate in the mitochondria of cancer cells (lung carcinomas). We will determine if the over-expression of specific heat-shock proteins in the mitochondria can protect cells from Photofrin®-mediated photodynamic therapy through protection of mitochondrial electron transport.

  14. Photodynamic therapy of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  15. Present status of photodynamic procedures in urology

    NASA Astrophysics Data System (ADS)

    Jocham, Dieter; Thomas, Stephen

    1994-03-01

    Since 1976, photodynamic therapy (PDT) has been used for the treatment of different stages of urothelial bladder tumors. First applications were based on the irradiation of single exophytic tumors using bare fibers for laser irradiation (630 mm) or bright white light generated e.g. from a mercury arc lamp. Clinical results of several centers demonstrated the possibility of destroying single superficially growing tumors. A new approach to the treatment of multifocal growing tumors, including the endoscopically often undetectable carcinoma in situ, was provided by the development of treatment modalities allowing for whole bladder wall irradiation. Photodynamic diagnosis (PDD) is a novel procedure for detecting flat precancerous and malignant lesions undetectable by endoscopy alone on the basis of laser- induced fluorescence.

  16. Second generation photodynamic agents: a review.

    PubMed

    Sternberg, E D; Dolphin, D

    1993-10-01

    Over the last decade, laser treatment of neoplastic diseases has become routine. The ability of these light-induced therapies to effect positive results is increased with the utilization of photosensitizing dyes. The approval of Photofrin in Canada as a first generation photodynamic therapeutic agent for the treatment of some forms of bladder cancer is being followed by the development of other agents with improved properties. At this time a number of second generation photosensitizing dyes are under study in phase I/II clinical trials. A review of the status of these trials along with mechanistic aspects is reviewed in this article. In addition, a review of the status of lasers to be utilized for photodynamic therapy gives some indication of which instruments could be considered for this therapy in the future. PMID:10146514

  17. Request for One-Time Shipment of 32 Watt PU-328 Source in 9968 Packaging

    SciTech Connect

    Massey, W.M.

    1998-11-25

    The 9968 package is designed for surface shipment of fissile and other radioactive materials where a high degree of double containment is required. The use of the 9968 radioactive material package for a one time shipment of a 32 watt heat source versus the SARP approved maximum 30 watt heat source is addressed in this report. The analyses show that the small increase in heat load from 30 watts to 32 watts does not substantially increase internal temperatures or pressures that would approach limits for the package. Also, the weight of the content is within the current 9968 package limits. It is concluded that the 32-watt heat source can be safely shipped in the 9968 package and therefore a waiver to ship the source is justified.

  18. Privacy-Preserving Authentication of Users with Smart Cards Using One-Time Credentials

    NASA Astrophysics Data System (ADS)

    Park, Jun-Cheol

    User privacy preservation is critical to prevent many sophisticated attacks that are based on the user's server access patterns and ID-related information. We propose a password-based user authentication scheme that provides strong privacy protection using one-time credentials. It eliminates the possibility of tracing a user's authentication history and hides the user's ID and password even from servers. In addition, it is resistant against user impersonation even if both a server's verification database and a user's smart card storage are disclosed. We also provide a revocation scheme for a user to promptly invalidate the user's credentials on a server when the user's smart card is compromised. The schemes use lightweight operations only such as computing hashes and bitwise XORs.

  19. Analysis of Forgery Attack on One-Time Proxy Signature and the Improvement

    NASA Astrophysics Data System (ADS)

    Wang, Tian-Yin; Wei, Zong-Li

    2016-02-01

    In a recent paper, Yang et al. (Quant. Inf. Process. 13(9), 2007-2016, 2014) analyzed the security of one-time proxy signature scheme Wang and Wei (Quant. Inf. Process. 11(2), 455-463, 2012) and pointed out that it cannot satisfy the security requirements of unforgeability and undeniability because an eavesdropper Eve can forge a valid proxy signature on a message chosen by herself. However, we find that the so-called proxy message-signature pair forged by Eve is issued by the proxy signer in fact, and anybody can obtain it as a requester, which means that the forgery attack is not considered as a successful attack. Therefore, the conclusion that this scheme cannot satisfy the security requirements of proxy signature against forging and denying is not appropriate in this sense. Finally, we study the reason for the misunderstanding and clarify the security requirements for proxy signatures.

  20. [Photodynamic therapy: non-oncologic indications].

    PubMed

    Karrer, S; Szeimies, R-M

    2007-07-01

    While efficacy of topical photodynamic therapy (PDT) for the treatment of superficial non-melanoma skin cancer is already well-proven by several controlled clinical trials, there are only a few controlled studies showing efficacy of PDT for non-oncologic skin disorders. This report provides information on the use of PDT for inflammatory skin disorders, disorders of the pilosebaceous unit, infections of the skin, sclerotic skin diseases and cosmetic indications. PMID:17546432

  1. Photodynamic therapy for occluded biliary metal stents

    NASA Astrophysics Data System (ADS)

    Roche, Joseph V. E.; Krasner, Neville; Sturgess, R.

    1999-02-01

    In this abstract we describe the use of photodynamic therapy (PDT) to recanalize occluded biliary metal stents. In patients with jaundice secondary to obstructed metal stents PDT was carried out 72 hours after the administration of m THPC. Red laser light at 652 nm was delivered endoscopically at an energy intensity of 50 J/cm. A week later endoscopic retrograde cholangiogram showed complete recanalization of the metal stent.

  2. Photodynamic therapy for pododermatitis in penguins.

    PubMed

    Sellera, Fábio Parra; Sabino, Caetano Padial; Ribeiro, Martha Simões; Fernandes, Loriê Tukamoto; Pogliani, Fabio Celidonio; Teixeira, Carlos Roberto; Dutra, Gustavo Henrique Pereira; Nascimento, Cristiane Lassálvia

    2014-01-01

    Pododermatitis is currently one of most frequent and important clinical complications in seabirds kept in captivity or in rehabilitation centers. In this study, five Magellanic penguins with previous pododermatitis lesions on their footpad were treated with photodynamic therapy (PDT). All PDT treated lesions successfully regressed and no recurrence was observed during the 6-month follow-up period. PDT seems to be an inexpensive and effective alternative treatment for pododermatitis in Magellanic penguins encouraging further research on this topic. PMID:24888264

  3. A one-time opportunity to expand the market for premium efficiency motors

    SciTech Connect

    Gordon, F.; Tumidaj, L.; Hoernlein, D.; Coakley, S.

    1997-07-01

    A mid-Atlantic utility conducted a detailed research study on their motors market. The study showed that their motor loads come mostly from motors under 50 horsepower, and predominantly from industry. The proportion of premium-efficiency motor sales is very low relative to other areas which, unlike this utility's service territory, have a history of rebate programs. Most sales in this utility's territory are for replacement motors. Manufacturers are planning to create new lines of motors which meet the 1997 federal minimum motor-efficiency manufacturing standard, but are less efficient than premium motors. Few of these motors are on the market yet. The mandatory federal efficiency standard creates a unique, one-time situation where premium-efficiency motors will be a better-established and more familiar product among customers and vendors than less efficient motors. The utility has begun a motors rebate and technical assistance program which is intended to use this one-time opportunity to significantly expand the market for premium motors. Rebates are tied to the new Consortium for Energy Efficiency motor standards to ensure a common message to manufacturers among utilities. While the majority of premium motors available locally already meet the standard, this will encourage manufacturers to bring the rest of their offerings in line. Like many motors programs, this program will offer rebates, marketing, and technical assistance. However, the program design calls for a short-term (three year), very intense effort, including a rebate set at 100% of incremental cost, a short-term vendor bonus, and intensive marketing to large customers. Additionally, the large savings per motor in 1997 (when the baseline is inefficient standard motors) will justify a more generous payment in the first year. Many other US utility motor rebate programs have offered less generous incentives and used less intensive marketing, but have had only marginal impacts on markets (often 20

  4. Photoangioplasty: new applications of photodynamic therapy in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Rockson, Stanley G.

    2000-05-01

    Atherosclerosis has traditionally held appeal as a pathologic entity in which photodynamic therapy might arrest or reverse the manifestations of disease. Earlier attempts to bring photodynamic therapy to the human clinical arena were hampered by the limitations of the photosensitizers under investigation, including the propensity to phototoxic manifestations and light-induced trauma to surrounding, normal vascular tissues. Many of these inherent limitations may be circumvented by newer photosensitizers that are activated at longer, more optimal wavelengths of light energy. Advances in fiberoptic catheter design for the endovascular delivery of light have also contributed to the greater applicability of photodynamic therapy to human atherosclerosis. Initial experiences with one family of photosensitizers, the texaphyrins, indicate that photodynamic therapy of human peripheral arterial atherosclerosis is feasible, safe, and well-tolerated. Photodynamic therapy of atherosclerosis holds promise for the treatment of de novo atherosclerosis and may have future applicability in the treatment, and perhaps prevention, of restenosis.

  5. Pulse mode of laser photodynamic treatment induced cell apoptosis.

    PubMed

    Klimenko, Vladimir V; Knyazev, Nickolay A; Moiseenko, Fedor V; Rusanov, Anatoliy A; Bogdanov, Alexey A; Dubina, Michael V

    2016-03-01

    One of the factors limiting photodynamic therapy (PDT) is hypoxia in tumor cells during photodynamic action. PDT with pulse mode irradiation and appropriate irradiation parameters could be more effective in the singlet oxygen generation and tissue re-oxygenation than continuous wave (CW) mode. We theoretically demonstrate differences between the cumulative singlet oxygen concentration in PDT using pulse mode and CW mode of laser irradiation. In vitro experimental results show that photodynamic treatment with pulse mode irradiation has similar cytotoxicity to CW mode and induces mainly cell apoptosis, whereas CW mode induces necrotic cell death. We assume that the cumulative singlet oxygen concentration and the temporal distribution of singlet oxygen are important in photodynamic cytotoxicity and apoptosis initiation. We expect our research may improve irradiation protocols and photodynamic therapy efficiency. PMID:26790610

  6. A 4-kbit low-cost antifuse one-time programmable memory macro for embedded applications

    NASA Astrophysics Data System (ADS)

    Xian, Li; Huicai, Zhong; Cheng, Jia; Xin, Li

    2014-05-01

    A 4-kbit low-cost one-time programmable (OTP) memory macro for embedded applications is designed and implemented in a 0.18-μm standard CMOS process. The area of the proposed 1.5 transistor (1.5T) OTP cell is 2.13 μm2, which is a 49.3% size reduction compared to the previously reported cells. The 1.5T cell is fabricated and measured and shows a large programming window without any disturbance. A novel high voltage switch (HVSW) circuit is also proposed to make sure the OTP macro, implemented in a standard CMOS process, works reliably with the high program voltage. The OTP macro is embedded in negative radio frequency identification (RFID) tags. The full chip size, including the analog front-end, digital controller and the 4-kbit OTP macro, is 600 × 600 μm2. The 4-kbit OTP macro only consumes 200 × 260 μm2. The measurement shows a 100% program yield by adjusting the program time and has obvious advantages in the core area and power consumption compared to the reported 3T and 2T OTP cores.

  7. Security enhanced optical one-time password authentication method by using digital holography

    NASA Astrophysics Data System (ADS)

    Gil, Sang Keun; Jeon, Seok Hee; Jeong, Jong Rae

    2015-03-01

    We propose a new optical one-time password(OTP) authentication method by using digital holography, which enhances security strength in the cryptosystem compared to the conventional electronic OTP method. In this paper, a challenge-response optical OTP authentication based on two-factor authentication is presented by 2-step quadrature phase-shifting digital holography using orthogonal polarization, and two-way authentication is also performed using the challenge-response handshake in both directions. The ID (identification), PW (password) and OTP information are encrypted with a shared key by applying phase-shifting digital holography, and these encrypted information are verified each other by the shared key. Because the encrypted digital holograms which are transmitted to the other party are expressed as random distribution, it guards against a replay attack and results in higher security level. Optically, encrypted digital hologram in our method is Fourier transform hologram and is recorded on CCD with 256 gray-level quantized intensities. The proposed method has an advantage that it does not need a time-synchronized OTP and can be applied to various security services. Computer experiments show that the proposed method is suitable for high secure OTP authentication.

  8. Vertically Stackable Novel One-Time Programmable Nonvolatile Memory Devices Based on Dielectric Breakdown Mechanism

    NASA Astrophysics Data System (ADS)

    Cho, Seongjae; Lee, Jung Hoon; Ryoo, Kyung-Chang; Jung, Sunghun; Lee, Jong-Ho; Park, Byung-Gook

    2011-12-01

    In this paper, a novel one-time programmable (OTP) nonvolatile memory (NVM) device and its array structures based on silicon technology are proposed. There have been many features of OTP NVM devices utilizing various combinations of channel, breakdown region, barrier, and contact materials. However, this invention can be realized by simple materials and fabrication methods: it is silicon-based materials and fully compatible with the conventional CMOS process. An individual memory cell is a silicon diode vertically integrated. Historically, OTP memories were widely used for read-only-memory (ROM) in the central processing unit (CPU) of the computer systems. By implanting the nanoscale fabrication technology into the concept of OTP memory, innovative high-density NVM appliances for massive storage media becomes very promising. The program operation is performed by breaking down the thin oxide layer between pn doped structure and wordline (WL) and its state can be sensed by the leakage current through the broken oxide. Since this invention is based on neither transistor structure nor charge-based mechanism, it is highly reliable and functional for the ultra-large scale integration. The feasibility of its stacked array will be also checked.

  9. One-time collision arbitration algorithm in radio-frequency identification based on the Manchester code

    NASA Astrophysics Data System (ADS)

    Liu, Chen-Chung; Chan, Yin-Tsung

    2011-02-01

    In radio-requency identification (RFID) systems, when multiple tags transmit data to a reader simultaneously, these data may collide and create unsuccessful identifications; hence, anticollision algorithms are needed to reduce collisions (collision cycles) to improve the tag identification speed. We propose a one-time collision arbitration algorithm to reduce both the number of collisions and the time consumption for tags' identification in RFID. The proposed algorithm uses Manchester coding to detect the locations of collided bits, uses the divide-and-conquer strategy to find the structure of colliding bits to generate 96-bit query strings as the 96-bit candidate query strings (96BCQSs), and uses query-tree anticollision schemes with 96BCQSs to identify tags. The performance analysis and experimental results show that the proposed algorithm has three advantages: (i) reducing the number of collisions to only one, so that the time complexity of tag identification is the simplest O(1), (ii) storing identified identification numbers (IDs) and the 96BCQSs in a register to save the used memory, and (iii) resulting in the number of bits transmitted by both the reader and tags being evidently less than the other algorithms in one-tag identification or in all tags identification.

  10. System requirements for one-time-use ENRAF control panel software

    SciTech Connect

    HUBER, J.H.

    1999-08-19

    An Enraf Densitometer is installed on tank 241-AY-102. The Densitometer will frequently be tasked to obtain and log density profiles. The activity can be effected a number of ways. Enraf Incorporated provides a software package called ''Logger18'' to its customers for the purpose of in-shop testing of their gauges. Logger18 is capable of accepting an input file which can direct the gauge to obtain a density profile for a given tank level and bottom limit. Logger18 is a complex, DOS based program which will require trained technicians and/or tank farm entries to obtain the data. ALARA considerations have prompted the development of a more user-friendly, computer-based interface to the Enraf densitometers. This document records the plan by which this new Enraf data acquisition software will be developed, reviewed, verified, and released. This plan applies to the development and implementation of a one-time-use software program, which will be called ''Enraf Control Panel.'' The software will be primarily used for remote operation of Enraf Densitometers for the purpose of obtaining and logging tank product density profiles.

  11. 75 FR 22805 - Submission for OMB Review; American Recovery and Reinvestment Act-One-Time Reporting Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ..., withdrawal. SUPPLEMENTARY INFORMATION: A. Background The Notice, published in the Federal Register at 75 FR...; American Recovery and Reinvestment Act--One-Time Reporting Requirements for Prime Contractors AGENCIES... Recovery and Reinvestment Act--One-time Reporting Requirements for Prime Contractors published in...

  12. 75 FR 17919 - Submission for OMB Review; American Recovery and Reinvestment Act-One-time Reporting Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... collection requirement concerning the American Recovery and Reinvestment Act--One-time Reporting Requirements for Prime Contractors. A request for public comments was published in the Federal Register at 74 FR...; American Recovery and Reinvestment Act--One-time Reporting Requirements for Prime Contractors...

  13. 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.

  14. In-office Painless Aminolevulinic Acid Photodynamic Therapy

    PubMed Central

    2016-01-01

    Objective: To evaluate the efficacy, safety, and pain of in-office “painless” aminolevulinic acid photodynamic therapy aimed at decreasing treatment-associated pain in patients undergoing removal of actinic keratoses. Design: Prospective split-face study comparing short aminolevulinic acid incubation times of 15 minutes followed by extended exposure (60 minutes) of continuous blue light versus conventional aminolevulinic acid photodynamic therapy. Prospective assessment of pain in patients undergoing in-office “painless” aminolevulinic acid photodynamic therapy. Setting: Clinical practice office. Participants: Three patients with actinic keratoses participated in the split-face study and 101 in the pain assessment study. Measurements: Evaluations in the split-face study included removal of actinic keratoses, skin temperature, and pain measured on a 10-point visual analog scale. Pain was assessed using the visual analog scale in the pain assessment study. Results: In the split-face study, in-office “painless” aminolevulinic acid photodynamic therapy resulted in a 52-percent reduction in lesions versus 44 percent for conventional aminolevulinic acid photodynamic therapy. Maximum pain scores of in-office “painless” aminolevulinic acid photodynamic therapy were all 0 at each time point, and the average score for conventional aminolevulinic acid photodynamic therapy was 7. Baseline skin temperatures increased from a baseline of 29 to 32°C to 34 to 35°C by minute 10 of blue light activation on both sides of the face. Results from the pain assessment study indicated no or minimal (scores 0-2) pain in nearly all patients who received in-office “painless” aminolevulinic acid photodynamic therapy as monotherapy or in combination with 5-fluoruacil or imiquimod used as pretreatments. Conclusions: In-office “painless” aminolevulinic acid photodynamic therapy appears to be effective for removing actinic keratoses and is associated with little or no pain

  15. Measurements Of Singlet Oxygen In Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Profio, A. E.; Shu, Kuang-Hsien

    1989-06-01

    Photochemical reactions are used in photodynamic therapy of cancer and other disease. The cytotoxic agent in photochemotherapy is usually singlet oxygen. Thus measurements of singlet oxygen production or concentration may allow prediction of the biological response. The decrease in fluorescence of L-tryptophan because of reaction with singlet oxygen, the decrease in absorbance of a dye such as RNO subject to secondary oxidation by singlet oxygen, and the decrease in fluorescence of the most common photosensitizer, dihematoporphyrin ether/ester (DHE) because of photobleaching, have been investigated in solutions in vitro. The most promising method for dosimetry and prediction of biological response appears to be the photobleaching of DHE.

  16. Endoscopic photodynamic therapy (PDT) for oesophageal cancer.

    PubMed

    Moghissi, Keyvan

    2006-06-01

    Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I-II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2mg/(kgbw) is administered 24-72h before endoscopic illumination using a Diode 630nm laser. Illumination may be either interstitial or intraluminal at a dose of 100-200J/cm. PMID:25049097

  17. 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.

  18. Photodynamic therapy and anti-tumour immunity

    PubMed Central

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

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  19. Photodynamic dosimetry in the treatment of periodontitis

    NASA Astrophysics Data System (ADS)

    Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

    2009-06-01

    Photodynamic therapy has been demonstrated to effectively kill human periopathogens in vitro. However, the translation of in vitro work to in vivo clinical efficacy has been difficult due to the number of variables present in any given patient. Parameters such as photosensitizer concentration, duration of light therapy and amount of light delivered to the target tissue all play a role in the dose response of PDT in vivo. In this 121 patient study we kept all parameters the same except for light dose which was delivered at either 150 mW or 220 mW. This clearly demonstrated the clinical benefits of a higher light dose in the treatment of periodontitis.

  20. Flexible textile light diffuser for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Selm, Barbel; Camenzind, Martin

    2005-03-01

    In this article a new medical application is introduced using textile production techniques to deliver a defined radiation dose. The advantage for photodynamic therapy (PDT) is that a flat luminous textile structure can homogeneously illuminate unequal body surfaces. The optical properties of this two-dimensional luminous pad are characterized with a set of bench-scale tests. In vitro investigations on petri dishes with cultivated cells and first clinical tests on animal patients are promising. In addition first measurement results are presented together with an outlook to future developments.

  1. 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.

  2. Photosensitizer and light diffusion through dentin in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Nogueira, Ana C.; Graciano, Ariane X.; Nagata, Juliana Y.; Fujimaki, Mitsue; Terada, Raquel S. S.; Bento, Antonio C.; Astrath, Nelson G. C.; Baesso, Mauro L.

    2013-05-01

    Photodynamic therapy has been considered a potential antimicrobial modality against oral infections, including dental caries. A model to estimate the penetration of both photosensitizers and light through human dentin, a factor of interest in photodynamic therapy, is proposed. The photoacoustic spectroscopy technique was used to evaluate in vitro dentin permeability of three different photosensitizers. Using the dentin optical absorption and scattering coefficients, it was possible to propose a semi-quantitative model predicting both photosensitizer and light doses within dentin. The graphic illustrations obtained provided guidelines that may be useful in photodynamic therapy protocols used as antimicrobial tools in caries lesions.

  3. Fighting fish parasites with photodynamically active chlorophyllin.

    PubMed

    Häder, D-P; Schmidl, J; Hilbig, R; Oberle, M; Wedekind, H; Richter, P

    2016-06-01

    Water-soluble chlorophyll (chlorophyllin) was used in a phototoxic reaction against a number of fish ectoparasites such as Ichtyobodo, Dactylogyrus, Trichodina, and Argulus. Chlorophyllin is applied to the water at concentrations of several micrograms per milliliter for a predefined incubation time, and afterwards, the parasites are exposed to simulated solar radiation. Application in the dark caused only little damage to the parasites; likewise, light exposure without the addition of the photosensitizer was ineffective. In Ichthyobodo, 2 μg/mL proved sufficient with subsequent simulated solar radiation to almost quantitatively kill the parasites, while in Dactylogyrus, a concentration of about 6 μg/mL was necessary. The LD50 value for this parasite was 1.02 μg/mL. Trichodina could be almost completely eliminated at 2 μg/mL. Only in the parasitic crustacean Argulus, no killing could be achieved by a photodynamic reaction using chlorophyllin. Chlorophyllin is non-toxic, biodegradable, and can be produced at low cost. Therefore, we propose that chlorophyllin (or other photodynamic substances) are a possible effective countermeasure against several ectoparasites in ponds and aquaculture since chemical remedies are either forbidden and/or ineffective. PMID:26936032

  4. 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

  5. Photodynamic-induced inactivation of Propionibacterium acnes

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Teschke, M.; Eick, Stephen G.; Pfister, W.; Meyer, Herbert; Halbhuber, Karl-Juergen

    1998-05-01

    We report on photodynamically induced inactivation of the skin bacterium Propionibacterium acnes (P. acnes) using endogenous as well as exogenous photosensitizers and red light sources. P. acnes is involved in the pathogenesis of the skin disease acne vulgaris. The skin bacterium is able to synthesize the metal-free fluorescent porphyrins protoporphyrin IX (PP) and coproporphyrin (CP) as shown by in situ spectrally-resolved detection of natural autofluorescence of human skin and bacteria colonies. These naturally occurring intracellular porphyrins act as efficient endogenous photosensitizers. Inactivation of P. acnes suspensions was achieved by irradiation with He-Ne laser light in the red spectral region (632.8 nm). We monitored the photodynamically-induced death of single bacteria using a fluorescent viability kit in combination with confocal laser scanning microscopy. In addition, the photo-induced inactivation was calculated by CFU (colony forming units) determination. We found 633 nm-induced inactivation (60 mW, 0.12 cm2 exposure area, 1 hour irradiation) of 72% in the case of non-incubated bacteria based on the destructive effect of singlet oxygen produced by red light excited endogenous porphyrins and subsequent energy transfer to molecular oxygen. In order to achieve a nearly complete inactivation within one exposure procedure, the exogenous photosensitizer Methylene Blue (Mb) was added. Far red exposure of Mb-labeled bacteria using a krypton ion laser at 647 nm and 676 nm resulted in 99% inactivation.

  6. 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.

  7. Inhibition of Endocytic Processes by Photodynamic Therapy

    PubMed Central

    Kessel, David

    2011-01-01

    Background and Objective Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: a murine leukemia, a murine hepatoma and a non-malignant epithelial cell line of human origin. Study Design/Materials and Methods The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the ‘flux’ of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal and endosomal photodamage were employed. Conclusions Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy. PMID:22057481

  8. Treatment of ichthyophthiriasis with photodynamically active chlorophyllin.

    PubMed

    Häder, D-P; Schmidl, J; Hilbig, R; Oberle, M; Wedekind, H; Richter, P R

    2016-04-01

    Water-soluble chlorophyll (chlorophyllin) exerts pronounced photodynamic activity on fish parasites. In order to determine its potential as a remedy against ectoparasites in fish carps were incubated in water with defined concentrations of chlorophyllin. The main focus of the experiments was on the ciliate Ichthyophthirius multifiliis (Fouquet) which is responsible for considerable losses in livestock in aquaculture. As malachite green, which in the past efficiently cured infected fishes, is banned because of its possible carcinogenicity; no effective remedy is presently available in aquaculture to treat ichthyophthiriasis. Using chlorophyllin, the number of trophonts was significantly reduced (more than 50 %) after 3 h incubation of infested fish at 2 and 4 mg/L and subsequent irradiation with simulated solar radiation. The lack of reinfection after light treatment indicates that also the remaining parasites have lost their multiplication capacity. In the controls (no chlorophyllin and no light, light but no chlorophyllin, or chlorophyllin but no light), no reduction of the I. multifiliis infection was observed. We propose that chlorophyllin (or other photodynamic substances) is a possible effective countermeasure against I. multifiliis and other ectoparasites in aquaculture. PMID:26693716

  9. Differential cell photosensitivity following porphyrin photodynamic therapy.

    PubMed

    Gomer, C J; Rucker, N; Murphree, A L

    1988-08-15

    Experiments were performed to determine if differences in porphyrin photosensitivity could be observed for cells with varying efficiency in DNA damage repair, as well as for cells which make up components of the vasculature. Photofrin II is undergoing current clinical evaluation for photodynamic therapy of solid tumors, and therefore the retention, dark toxicity, and photosensitizing effects of this drug on human DNA repair-deficient fibroblasts (ataxia telangiectasia and xeroderma pigmentosum) were compared to normal human fibroblasts. In addition, bovine cells of endothelial, smooth muscle, and fibroblast origin were compared for porphyrin retention, toxicity, and photosensitivity. All human fibroblasts exhibited porphyrin-induced dark toxicity, but there were no significant differences in photosensitization or porphyrin retention for any of these cell lines. However, bovine endothelial cells were considerably more photosensitive than smooth muscle or fibroblast cells treated under identical conditions. All bovine cells accumulated similar levels of porphyrin, and therefore the increased sensitivity of the endothelial cells was not due to differences in porphyrin retention. These results provide additional evidence that nuclear damage and/or repair is not a dominant factor in the cytotoxicity induced by porphyrin photosensitization. In addition, these results indicate that endothelial cell photosensitivity may play a role in the vascular damage observed following photodynamic therapy. PMID:2969280

  10. Role of multidrug resistance in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Diddens, Heyke C.

    1992-06-01

    Multidrug resistance in cancer chemotherapy is a well established phenomenon. One of the most common phenotypical changes in acquired or intrinsic multidrug resistance in human tumor cells is the overexpression of the mdrl gene product P-glycoprotein, which acts as an active efflux pump. Increased levels of P-glycoprotein are associated with resistance to a variety of anticancer drugs commonly used in tumor chemotherapy like anthracyclins, vinca- alcaloids, epipodophyllotoxins or actinomycin D. We investigated the efficacy or photodynamic therapy in the treatment of tumor cells expressing the multidrug resistance phenotype. Our data show that multidrug resistant cells are highly cross resistant to the phototoxic stain rhodamine 123 but exhibit only low degrees of cross resistance (2 - 3 -folds) to the photosensitizers Photosan-3, Clorin-2, methylene blue and meso-tetra (4- sulfonatophenyl) porphine (TPPS4). Resistance is associated with a decrease in intracellular accumulation of the photosensitizer. Verapamil, a membrane active compound known to enhance drug sensitivity in multidrug resistant cells by inhibition of P-glycoprotein, also increases phototoxicity in multidrug resistant cells. Our results imply that tumors expressing the multidrug resistance phenotype might fail to respond to photochemotherapy with rhodamine 123. On the other hand, multidrug resistance may not play an important role in photodynamic therapy with Photosan-3, Chlorin-2, methylene blue or TPPS4.

  11. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies

    PubMed Central

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-01

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve. PMID:26805818

  12. Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

    NASA Astrophysics Data System (ADS)

    Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

    2016-03-01

    Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

  13. Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum*

    PubMed Central

    Ramos, Rogério Rodrigo; Kozusny-Andreani, Dora Inês; Fernandes, Adjaci Uchôa; Baptista, Mauricio da Silva

    2016-01-01

    BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID:27192510

  14. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies.

    PubMed

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-01

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve. PMID:26805818

  15. Ozone-photodynamic effect in the experiment in vitro

    NASA Astrophysics Data System (ADS)

    Loginov, L. E.; Budzinsky, A. A.; Torshina, Nadezgda L.; Posypanova, Anna M.; Volkova, Anna I.

    1996-12-01

    With the purpose of increased photodestruction oncocells we develop a method of ozone-photodynamic therapy. As a target cell for laser processing we are using photosensibilitable erythrocytes of integral blood patient, past seance of ozonetherapy.

  16. Photodynamic/photocatalytic effects on microorganisms processed by nanodyes

    NASA Astrophysics Data System (ADS)

    Tuchina, Elena S.; Tuchin, Valery V.

    2010-02-01

    Photodynamic therapy uses laser, LED or lamp light sources in combination with dyes - exogenous photosensitizers for the enhancement and localization of photodynamic effects within the human body. We are developing a new approach of improvement of the efficiency of antimicrobial phototherapy via combined application of photosensitizers and the photocatalysts to pathogenic microorganisms. The main goal of the paper is to conduct experiments to study the action of nanodyes, based on mixtures of nanoparticles and photosensitizers, in combination with LED irradiation of pathogens.

  17. Inhibiton of photodynamic haemolysis by Gratiola officinalis L. extract

    NASA Astrophysics Data System (ADS)

    Tkachenko, Natalie; Pravdin, Alexander; Terentyuk, George; Navolokin, Nikita; Kurchatova, Maria; Polukonova, Natalia

    2015-03-01

    On the model of photodynamic haemolysis, the membranoprotective properties of a plant origin antioxidant, Gratiola officinalis L. extract, have been studied based on its ability to inhibit photodamage of sensitized erythrocyte membranes. The effect of different concentrations of the antioxidant on the photodynamic hemolysis has been studied; and the influence of incubation time on the membranoprotective properties of Gratiola officinalis L. extract has also been revealed.

  18. Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

    NASA Astrophysics Data System (ADS)

    Kato, Ilka Tiemy; Prates, Renato Araujo; Tegos, George P.; Hamblin, Michael R.; Simões Ribeiro, Martha

    2011-03-01

    Photodynamic antimicrobial chemotherapy (PACT) is based on the principal that microorganisms will be inactivated using a light source combined to a photosensitizing agent in the presence of oxygen. Oxidative damage of cell components occurs by the action of reactive oxygen species leading to cell death for microbial species. It has been demonstrated that PACT is highly efficient in vitro against a wide range of pathogens, however, there is limited information for its in vivo potential. In addition, it has been demonstrated that sublethal photodynamic inactivation may alter the virulence determinants of microorganisms. In this study, we explored the effect of sublethal photodynamic inactivation to the virulence factors of Candida albicans. Methylene Blue (MB) was used as photosensitizer for sublethal photodynamic challenge on C. albicans associated with a diode laser irradiation (λ=660nm). The parameters of irradiation were selected in causing no reduction of viable cells. The potential effects of PACT on virulence determinants of C. albicans cells were investigated by analysis of germ tube formation and in vivo pathogenicity assays. Systemic infection was induced in mice by the injection of fungal suspension in the lateral caudal vein. C. albicans exposed to sublethal photodynamic inactivation formed significantly less germ tube than untreated cells. In addition, mice infected with C. albicans submitted to sublethal PACT survived for a longer period of time than mice infected with untreated cells. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence determinants and reduced in vivo pathogenicity of C. albicans.

  19. Photodynamic Cancer Therapy—Recent Advances

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2011-09-01

    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

  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. Photodynamic therapy as an antifungal treatment

    PubMed Central

    LIANG, YI; LU, LI-MING; CHEN, YONG; LIN, YOU-KUN

    2016-01-01

    Photodynamic therapy (PDT) involves the systemic or topical application of a photosensitizer (PS), alongside the selective illumination of the target lesion with light of an appropriate wavelength, in order to promote localized oxidative photodamage and subsequent cell death. Numerous studies have demonstrated that PDT is highly effective in the destruction of fungi in vitro. The mechanism underlying the effects of PDT results from the photons of visible light of an appropriate wavelength interacting with the intracellular molecules of the PS. Reactive species are produced as a result of the oxidative stress caused by the interaction between the visible light and the biological tissue. At present, no antifungal treatment based on PDT has been licensed. However, antifungal PDT is emerging as an area of interest for research. PMID:27347012

  2. Irradiation system for interstitial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Pacheco, L.; Stolik, S.; De la Rosa, J.

    2013-11-01

    Interstitial Photodynamic Therapy (IPDT) is a promising form of treatment of deep-seated and bulky malignant tumors, based on the lethal cell response to the photochemical reactions when drug is light activated in presence of oxygen. In order to accomplish an effective internal illumination, laser sources are preferably used because of two important reasons: the monochromatic light can be confined to the narrow absorption band of the drug and the laser beam is easily focused into optical fibers. In this work the development of a diode-laser-light-source is presented. The system is tuned by temperature to get a better match in the 5-ALA absorption band. This system also comprises a trifurcated fiber system to accomplish interstitial illumination.

  3. Mechanism of photodynamic activity of pheophorbides

    NASA Astrophysics Data System (ADS)

    Tanielian, Charles; Kobayashi, Masami; Wolff, Christian

    2001-04-01

    Plasmid DNA is efficiently photocleaved by sodium pheophorbides (Na-Phdes) a and b in the absence of oxygen as well as in the presence of oxygen. Fluorescence microscopic observation shows a rapid incorporation of Na-Phde a into nuclei, mitochondria, and lysosome of human oral mucosa cells. In contrast Na-Phde b is incorporated only into the plasma membrane. The photodynamic activity of these pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures and involves two types of reactions: (1) direct electron transfer between DNA bases (especially guanine) and pheophorbide singlet excited state, and (2) indirect reactions medicated by reactive oxygen species, including singlet oxygen whose production from molecular oxygen is sensitized by the Na-Phdes triplet state.

  4. 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

  5. Dosimetry for photodynamic therapy of endometrial tissue

    NASA Astrophysics Data System (ADS)

    Svaasand, Lars O.; Fehr, Mathias K.; Madsen, Sten; Tadir, Yona; Tromberg, Bruce J.

    1995-05-01

    Hysterectomy is the most common major operation performed in the United States with dysfunctional uterine bleeding as one of the major indications. The clinical needs for simple and safe endometrial destruction are essential. Photodynamic therapy (PDT) may offer a simple and cost effective solution for the treatment of dysfunctional uterine bleeding. The dosimetry is discussed for the case of topical application of photosensitizer. This technique might be the method of preference because undesired side effects such as skin photosensitization that is typical for systemically injected photosensitizers, can be avoided. Effective PDT requires a sufficient amount of light delivered to the targeted tissue in a reasonable period of time. A trifurcated optical applicator consisting of three cylindrical diffusing fibers has been constructed, and this applicator can deliver a typical required optical dose of about 50-100 J/cm2 to the full depth of the endometrium for an exposure time of 10-20 minutes.

  6. Monitoring photodynamic therapy with photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Shao, Peng; Chapman, David W.; Moore, Ronald B.; Zemp, Roger J.

    2015-10-01

    We present our work on examining the feasibility of monitoring photodynamic therapy (PDT)-induced vasculature change with acoustic-resolution photoacoustic microscopy (PAM). Verteporfin, an FDA-approved photosensitizer for clinical PDT, was utilized. With a 60-μm-resolution PAM system, we demonstrated the capability of PAM to monitor PDT-induced vasculature variations in a chick chorioallantoic membrane model with topical application and in a rat ear with intravenous injection of the photosensitizer. We also showed oxygen saturation change in target blood vessels due to PDT. Success of the present approach may potentially lead to the application of PAM imaging in evaluating PDT efficacy, guiding treatment, and predicting responders from nonresponders.

  7. Death pathways associated with photodynamic therapy

    PubMed Central

    Kessel, David

    2009-01-01

    When the mitochondria and/or the endoplasmic reticulum were targeted by photodynamic therapy, photodamage to the anti-apoptotic protein Bcl-2 was observed. This led to an apoptotic outcome if that death pathway was available. Lysosomal photodamage ultimately resulted in activation of the pro-apoptotic protein Bid, also leading to apoptosis. Photodamage to the plasma membrane was associated with migration of sensitizers to the cytosol and procaspase photodamage, with apoptosis impaired. Where apoptosis was unavailable because of lack of necessary components of the program, an autophagic outcome has been observed. It is also clear that autophagy can occur along with apoptosis as a PDT response, and may play a role in immunologic responses to photodamaged tumor cells. PMID:19890442

  8. Initiation of Autophagy by Photodynamic Therapy

    PubMed Central

    Kessel, David; Oleinick, Nancy L.

    2010-01-01

    Photodynamic therapy (PDT) involves the irradiation of photosensitized cells with light. Depending on localization of the photosensitizing agent, the process can induce photodamage to the endoplasmic reticulum (ER), mitochondria, plasma membrane, and/or lysosomes. When ER or mitochondria are targeted, antiapoptotic proteins of the Bcl-2 family are especially sensitive to photodamage. Both apoptosis and autophagy can occur after PDT, autophagy being associated with enhanced survival at low levels of photodamage to some cells. Autophagy can become a cell-death pathway if apoptosis is inhibited or when cells attempt to recycle damaged constituents beyond their capacity for recovery. While techniques associated with characterization of autophagy are generally applicable, PDT introduces additional factors related to unknown sites of photodamage that may alter autophagic pathways. This chapter discusses issues that may arise in assessing autophagy after cellular photodamage. PMID:19216899

  9. 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

  10. Progress of Photodynamic Therapy in Gastric Cancer

    PubMed Central

    Narahara, Hiroyuki; Otani, Toru; Okuda, Shigeru

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm2 for an argon dye laser and 60 J/cm2 for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm2 in area to 4 cm in diameter, i.e. 13 cm2 by employing a new excimer dye laser model, which could emit 4mJ/pulse with 80 Hz pulse frequency. (4) The depth of cancer invasion which could be treated by PDT was increased from about 4 mm, i.e. the superficial part of the submucosal layer (SM-1) to more than 10 mm in depth, i.e. the proper muscular layer. These improvements owe much to the pulse laser, the photodynamic action induced by which permits deeper penetration than that of a continuous wave laser. (5) We employed a side-viewing fiberscope for gastric PDT to irradiate the lesion from an angle of 90°. (6) We designed a simple cut quartz fiber for photoradiation with a spiral spring thickened toward the end. (7) We developed an endoscopic device for photoradiation in PDT which achieves accurate and efficient irradiation. As a result of these improvements a higher cure rate was obtained even with a lower light dose of irradiation. PMID:18493500

  11. Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

    PubMed Central

    Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

    2014-01-01

    Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

  12. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part five of a five-part series

    PubMed Central

    2009-01-01

    The use of 5-aminolevulinic acid–photodynamic therapy in clinical practice is an individual determination based on experiences learned from clinicians and from personal experience. This manuscript reviews how one clinician approaches patients interested in having photodynamic therapy. It covers all practical aspects of the treatment process and reviews how photodynamic therapy can be utilized in your clinical practice. PMID:20967186

  13. Quantum Cryptography II: How to re-use a one-time pad safely even if P=NP.

    PubMed

    Bennett, Charles H; Brassard, Gilles; Breidbart, Seth

    2014-01-01

    When elementary quantum systems, such as polarized photons, are used to transmit digital information, the uncertainty principle gives rise to novel cryptographic phenomena unachievable with traditional transmission media, e.g. a communications channel on which it is impossible in principle to eavesdrop without a high probability of being detected. With such a channel, a one-time pad can safely be reused many times as long as no eavesdrop is detected, and, planning ahead, part of the capacity of these uncompromised transmissions can be used to send fresh random bits with which to replace the one-time pad when an eavesdrop finally is detected. Unlike other schemes for stretching a one-time pad, this scheme does not depend on complexity-theoretic assumptions such as the difficulty of factoring. PMID:25400534

  14. 75 FR 9997 - Bureau of Educational and Cultural Affairs (ECA) Request for Grant Proposals (RFGP): One-time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    ... Grants Program-- Competition A--Academic Programs Announcement Type: New Grant Funding Opportunity Number... Program'' is $8 million. Four million dollars will be dedicated to Competition A--Academic Programs One... The Office of Academic Programs will accept proposals for the following one-time special...

  15. Mitochondria-targeting for improved photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ngen, Ethel J.

    Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus

  16. Graphene-based nanovehicles for photodynamic medical therapy.

    PubMed

    Li, Yan; Dong, Haiqing; Li, Yongyong; Shi, Donglu

    2015-01-01

    Graphene and its derivatives such as graphene oxide (GO) have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review. PMID:25848263

  17. Graphene-based nanovehicles for photodynamic medical therapy

    PubMed Central

    Li, Yan; Dong, Haiqing; Li, Yongyong; Shi, Donglu

    2015-01-01

    Graphene and its derivatives such as graphene oxide (GO) have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review. PMID:25848263

  18. Photodynamic therapy: Biophysical mechanisms and molecular responses

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya

    In photodynamic therapy (PDT), photochemical reactions induced by optical activation of sensitizer molecules cause destruction of the target tissue. In this thesis we present results of several related studies, which investigated the influence of photophysical properties and photobleaching mechanisms of sensitizers and oxygen-dependent tissue optical properties on PDT treatment efficacy. The bleaching mechanism of the sensitizer meso-tetra hydroxyphenyl chlorin (mTHPC) is examined indirectly using measurements of photochemical oxygen consumption during PDT irradiation of multicell tumor spheroids. Analysis of the results with a theoretical model of oxygen diffusion that incorporates the effects of sensitizer photobleaching shows that mTHPC is degraded via a singlet-oxygen (1O2)-mediated bleaching process. The analysis allows us to extract photophysical parameters of mTHPC which are used to account for its enhanced clinical photodynamic potency in comparison to that of Photofrin. Evaluation of the spatially-resolved fluorescence in confocal optical sections of intact spheroids during PDT irradiation allows for the direct experimental verification of mTHPC's 1O2-mediated bleaching mechanism. The technique is also used to investigate the complex bleaching kinetics of Photofrin. The results allow us to successfully reconcile apparently contradictory experimental observations and to confirm the predictions of a new theoretical model in which both 1O2 and excited triplet sensitizer molecules are allowed to contribute to photobleaching. Based on studies performed in tissue-simulating erythrocyte phantoms and in a murine tumor model in vivo, we present clinically relevant results which indicate that a shift toward increased hemoglobin-oxygen saturation due to improved tissue oxygenation reduces PDT treatment beam attenuation and may allow for more effective treatment of deeper lesions. Finally, we investigate the induction of the stress protein, heat shock protein 70 (HSP

  19. Photodynamic therapy for treatment of head and neck cancer.

    PubMed

    Schweitzer, V G

    1990-03-01

    Since 1975, photodynamic therapy has reportedly been effective in a variety of head and neck malignancies that failed traditional (conventional) therapy, including surgery, cryotherapy, chemotherapy, hyperthermia, and radiation therapy. Photodynamic therapy consists of the intravenous administration of (di)hematoporphyrin ether, a chemosensitizing drug selectively retained by neoplastic and reticuloendothelial tissues which, when exposed to a 630-nm argon laser, catalyzes a photochemical reaction to release free oxygen radicals, "the cytotoxic" agents responsible for cell death and tumor necrosis. Preliminary investigations have assessed the efficacy of photodynamic therapy in treatment of: (1) superficial "condemned mucosa" or "field cancerization" of the oral cavity and (2) stage III and IV head and neck carcinomas that had unsuccessful conventional therapy. Complete and/or partial remissions were obtained in 11 of 12 patients (16 treatments) with a variety of carcinomas of the nasopharynx, palate and uvula, retromolar trigone, temporal bone, cervical esophagus, and AIDS-related Kaposi's sarcoma of the oral cavity. PMID:2108409

  20. Nitrosylhemoglobin in photodynamically stressed human tumors growing in nude mice.

    PubMed

    Jakubowska, Monika; Michalczyk-Wetula, Dominika; Pyka, Janusz; Susz, Anna; Urbanska, Krystyna; Płonka, Beata K; Kuleta, Patryk; Łącki, Piotr; Krzykawska-Serda, Martyna; Fiedor, Leszek; Płonka, Przemysław M

    2013-11-30

    The role of nitric oxide in human tumor biology and therapy has been the subject of extensive studies. However, there is only limited knowledge about the mechanisms of NO production and its metabolism, and about the role NO can play in modern therapeutic procedures, such as photodynamic therapy. Here, for the first time, we report the presence of nitrosylhemoglobin, a stable complex of NO, in human lung adenocarcinoma A549 tumors growing in situ in nude mice. Using electron paramagnetic resonance spectroscopy we show that the level of nitrosylhemoglobin increases in the course of photodynamic therapy and that the phenomenon is local. Even the destruction of strongly vascularized normal liver tissue did not induce the paramagnetic signal, despite bringing about tissue necrosis. We conclude that photodynamic stress substantiates NO production and blood extravasation in situ, both processes on-going even in non-treated tumors, although at a lower intensity. PMID:23973529

  1. 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.

  2. Effects of Methane-Rich Saline on the Capability of One-Time Exhaustive Exercise in Male SD Rats

    PubMed Central

    Xin, Lei; Sun, Xuejun; Lou, Shujie

    2016-01-01

    Purpose To explore the effects of methane-rich saline (CH4 saline) on the capability of one-time exhaustive exercise in male SD rats. Methods Thirty rats were equally divided into to three groups at random: control group (C), placebo group (P) and methane saline group (M). Rats in M group underwent intraperitoneal injection of CH4 saline, and the other two groups simultaneously underwent intraperitoneal injection of normal saline. Then, the exercise capability of rats was tested through one-time exhaustive treadmill exercise except C group. Exercise time and body weight were recorded before and after one-time exhaustive exercise. After exhaustive exercise, the blood and gastrocnemius samples were collected from all rats to detect biochemical parameters in different methods. Results It was found that the treadmill running time was significantly longer in rats treated with CH4 saline. At the same time, CH4 saline reduced the elevation of LD and UN in blood caused by one-time exhaustive exercise. The low level of blood glucose induced by exhaustive exercise was also normalized by CH4 saline. Also CH4 saline lowered the level of CK in plasma. Furthermore, this research indicated that CH4 saline markedly increased the volume of T-AOC in plasma and alleviated the peak of TNF-α in both plasma and gastrocnemius. From H&E staining, CH4 saline effectively improved exercise-induced structural damage in gastrocnemius. Conclusions CH4 saline could enhance exercise capacity in male SD rats through increase of glucose aerobic oxidation, improvement of metabolic clearance and decrease of exhaustive exercise-induced gastrocnemius injury. PMID:26942576

  3. 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.

  4. Photodynamic therapy of malignant mesothelioma of pleura

    NASA Astrophysics Data System (ADS)

    Warloe, Trond; Heyerdahl, Helen; Peng, Qian; Hoie, J.; Normann, E.; Solheim, O.; Moan, Johan; Giercksky, Karl-Erik

    1995-03-01

    Nine patients with malignant pleural mesothelioma underwent extensive surgery followed by intra-operative photodynamic therapy. Two mg/kg Photofrin was given 48 hours prior to surgery. The thoracic cavity and eventual remaining lung were exposed to 15 - 30 Joules/cm2 of 630 nm laser light. Tumor tissue was analyzed by microscopic photometrical techniques. Five patients with mixed or epithelioid tumors with fluorescence intensity > 100 gray level/pixel seemed to benefit from the given therapy. One patient was free of disease 18 months after treatment. Two patients were treated for metastasis after 12 months with no sign of intrathoracic recurrence. Both are still alive, one without further sign of disease 32 months after initial treatment. Two patients presented generalized disease after 9 and 13 months and intrathoracic recurrence several months later. Two patients with poorly differentiated tumors and 2 patients with moderate to highly differentiated tumors, but with fluorescence intensity < 100 gray level/pixel, presented recurrences after 4 months. PDT-efficiency seems to be predicted by the intensity and distribution of drug-induced fluorescence in tumor tissue. PDT may enhance the possibility to achieve complete local tumor control after excision. Multimodal therapeutic approach of local and systemic disease seems mandatory to further improve survival.

  5. Variables in photodynamic therapy for Barrett's esophagus

    NASA Astrophysics Data System (ADS)

    Jones, Linda R.; Preyer, Norris W.; Buchanan, Jane; Reynolds, Daryl M.; Wolfsen, Herbert C.; Wallace, Michael B.; Gill, Kanwar R. S.

    2009-06-01

    Photodynamic therapy with porfimer sodium (PS) is a treatment option for high grade dysplasia associated with Barrett's esophagus. This study sought to investigate the optical properties of Barrett's dysplasia that may be useful in light dosimetry planning and to determine the effect of PS on tissue absorption and scattering. Fiber optic reflectance spectra were collected before and 48 hours after administration of 2 mg/kg PS. Mucosal biopsies were collected at the same locations. According to Monte Carlo analysis, the fiber optic probe sampled only the mucosal layer. A mathematical fit of the reflectance spectra was performed as a function of blood volume fraction, oxygen saturation and scattering. The average calculated blood volume was 100% higher in Barrett's tissue than normal esophageal tissue. The average scattering slope from 620 to 750 nm was 26% higher for Barrett's dysplasia than normal esophageal tissue, indicating an increase in the size of scattering particles. The difference in the scattering amplitude was not statistically significant, suggesting no significant increase in the number of scattering particles. PS tissue content was determined with extraction methods. Changes in the scattering slope due to PS sensitization were observed; however they were not proportional to the extracted PS concentration.

  6. PDT dose dosimeter for pleural photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.

    2016-03-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry.

  7. Photodynamic therapy of recurrent cerebral glioma

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

    Photodynamic therapy (PDT) was performed on 11 cases of recurrent cerebral glioma, including 3 cases of recurrent glioblastoma, 7 of recurrent anaplastic astrocytoma, and 1 recurrent ependymoma. Hematoporphyrin derivative (HPD) was administered intravenously at a dose of 4 - 7 mg/kg 5 - 24 hours before the operation. All patients underwent a craniotomy with a nearly radical excision of the tumor following which the tumor bed was irradiated with 630 nm laser light emitting either an argon pumped dye laser or frequency double YAG pumped dye laser for 30 to 80 minutes with a total dose of 50 J/cm2 (n equals 1), 100 J/cm2 (n equals 2), 200 J/cm2 (n equals 7), and 300 J/cm2 (n equals 1). The temperature was kept below 37 degree(s)C by irrigation. Two patients underwent postoperative radiotherapy. There was no evidence of increased cerebral edema, and no other toxicity by the therapy. All patients were discharged from the hospital within 15 days after surgery. We conclude that PDT using 4 - 7 mg/kg of HPD and 630 nm light with a dose of up to 300 J/cm2 can be used as an adjuvant therapy with no additional complications. Adjuvant PDT in the treatment of recurrent glioma is better than simple surgery.

  8. Photodynamic Antimicrobial Polymers for Infection Control

    PubMed Central

    McCoy, Colin P.; O’Neil, Edward J.; Cowley, John F.; Carson, Louise; De Baróid, Áine T.; Gdowski, Greg T.; Gorman, Sean P.; Jones, David S.

    2014-01-01

    Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting. PMID:25250740

  9. Photodynamic therapy in head and neck cancer.

    PubMed

    Nelke, Kamil H; Pawlak, Wojciech; Leszczyszyn, Jarosław; Gerber, Hanna

    2014-01-01

    Photodynamic therapy (PDT) is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC), and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages. PMID:24491903

  10. Palliation of esophageal malignancy with photodynamic therapy.

    PubMed

    McCaughan, J S; Williams, T E; Bethel, B H

    1985-08-01

    Sixteen patients with esophageal malignancies received photodynamic therapy after 3 mg of hematoporphyrin derivative (Photofrin I) or 2 mg of Photofrin II per kilogram of body weight was injected intravenously two to six days prior to treatment. A tunable dye argon laser system delivered 630 nm light through quartz fibers passed through the biopsy channel of a gastroscope. All patients obtained improvement in swallowing, usually from total obstruction or clear liquids only to a regular diet within three weeks and with new techniques, at least liquids within three days of treatment. Karnofsky Performance Status (KPS) and esophageal grades were measured before treatment, 1 month following treatment, and periodically until death. Ten patients died an average of 3.7 months after initial treatment (range, 0.6 to 19 months). Six patients are alive at 11, 10, 5, 2.5, 2 months, and 1 month after treatment. The median survival of 12 patients treated more than 6 months ago was 6.5 months and of 9 patients with an initial KPS higher than 30, 8.1 months. PMID:2411233

  11. Photodynamic inactivation of pathogens causing infectious keratitis

    NASA Astrophysics Data System (ADS)

    Simon, Carole; Wolf, G.; Walther, M.; Winkler, K.; Finke, M.; Hüttenberger, D.; Bischoff, Markus; Seitz, B.; Cullum, J.; Foth, H.-J.

    2014-03-01

    The increasing prevalence of antibiotic resistance requires new approaches also for the treatment of infectious keratitis. Photodynamic Inactivation (PDI) using the photosensitizer (PS) Chlorin e6 (Ce6) was investigated as an alternative to antibiotic treatment. An in-vitro cornea model was established using porcine eyes. The uptake of Ce6 by bacteria and the diffusion of the PS in the individual layers of corneal tissue were investigated by fluorescence. After removal of the cornea's epithelium Ce6-concentrations < 1 mM were sufficient to reach a penetration depth of 500 μm. Liquid cultures of microorganisms were irradiated using a specially constructed illumination chamber made of Spectralon(R) (reflectance: 99 %), which was equipped with high power light emitting diodes (λ = 670 nm). Clinical isolates of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) from keratitis patients were tested in liquid culture against different concentrations of Ce6 (1 - 512 μM) using 10 minutes irradiation (E = 18 J/cm2 ). This demonstrated that a complete inactivation of the pathogen strains were feasible whereby SA was slightly more susceptible than PA. 3909 mutants of the Keio collection of Escherichia coli (E.coli) were screened for potential resistance factors. The sensitive mutants can be grouped into three categories: transport mutants, mutants in lipopolysaccharide synthesis and mutants in the bacterial SOS-response. In conclusion PDI is seen as a promising therapy concept for infectious keratitis.

  12. Melanoma resistance to photodynamic therapy: new insights

    PubMed Central

    Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.

    2012-01-01

    Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor. PMID:23152406

  13. Photodynamic antibacterial effect of graphene quantum dots.

    PubMed

    Ristic, Biljana Z; Milenkovic, Marina M; Dakic, Ivana R; Todorovic-Markovic, Biljana M; Milosavljevic, Momir S; Budimir, Milica D; Paunovic, Verica G; Dramicanin, Miroslav D; Markovic, Zoran M; Trajkovic, Vladimir S

    2014-05-01

    Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD. PMID:24612819

  14. Progress in photodynamic therapy on tumors

    NASA Astrophysics Data System (ADS)

    Tian, Y. Y.; Wang, L. L.; Wang, W.

    2008-10-01

    Photodynamic therapy (PDT) is a promising treatment on neoplastic pathologic tissues, which involves the administration of a photosensitizing agent followed by the exposure of the tissue to visible nonthermal light. Light energy is captured and transferred to other molecules resulting in the formation of short-lived energetic species, which interact with biological systems and then produce tissue damage. Photosensitizer can be taken up selectively by tumor cells because of the upregulation of low-density lipoprotein receptor-mediated endocytosis and the acidic tumor environments. In recent years, the application of PDT in the treatment of malignant lesions has increased dramatically. The first health agency approval for PDT was granted for Photofrin in Canada in 1993, and, now, it is licensed in many countries for the treatment of cancers. Although Photofrin is the most commonly used photosensitizer, it has significant side effects. Therefore, major effort has been invested in the development of new sensitizers and, to this end, many photosensitizers have been described and some are now in clinical trials.

  15. Light emitting fabric technologies for photodynamic therapy.

    PubMed

    Mordon, Serge; Cochrane, Cédric; Tylcz, Jean Baptiste; Betrouni, Nacim; Mortier, Laurent; Koncar, Vladan

    2015-03-01

    Photodynamic therapy (PDT) is considered to be a promising method for treating various types of cancer. A homogeneous and reproducible illumination during clinical PDT plays a determinant role in preventing under- or over-treatment. The development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of optical fiber into flexible structures could offer an interesting alternative. This paper aims to describe different methods proposed to develop Side Emitting Optical Fibers (SEOF), and how these SEOF can be integrated in a flexible structure to improve light illumination of the skin during PDT. Four main techniques can be described: (i) light blanket integrating side-glowing optical fibers, (ii) light emitting panel composed of SEOF obtained by micro-perforations of the cladding, (iii) embroidery-based light emitting fabric, and (iv) woven-based light emitting fabric. Woven-based light emitting fabrics give the best performances: higher fluence rate, best homogeneity of light delivery, good flexibility. PMID:25481663

  16. 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

  17. 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

  18. Photodynamic therapy in lung and gastrointestinal cancers.

    PubMed

    Karanov, S; Kostadinov, D; Shopova, M; Kurtev, P

    1990-06-01

    Twelve central bronchial carcinoma patients and two gastrointestinal (GI) tract (oesophageal and colonic) early-stage cancer patients were treated with photodynamic therapy (PDT). Haematoporphyrin (HP/5, Jacopo Monico, Italy) at a dose of 5 mg kg-1 body weight was used as photosensitizer. Laser light at 628.2-630 nm generated by two different laser systems (gold vapour laser (I.P. Optics, Sofia, Bulgaria) in lung cancer cases and an argon dye laser system (Spectra Physics, Mountain View, U.S.A.) in GI tract cancers) was used. Lung cancers were irradiated 48 h after drug administration and GI tract cancers were irradiated 72 h after infusion of the photosensitizer. Both tumour sites were treated with a total energy dose in the range 350-600 J cm-2. Efficiency of PDT in lung cancer was evaluated by X-rays and endoscopic and functional respiratory tests for bronchial de-obstruction. Complete remission after PDT of GI tract cancers was considered to be tumour eradication (histologically and cytologically proved) and a tumour-free interval of at least 12 months. PMID:2121932

  19. PDT Dose Dosimeter for Pleural Photodynamic Therapy

    PubMed Central

    Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.

    2016-01-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry. PMID:27053825

  20. 5-ALA based photodynamic management of glioblastoma

    NASA Astrophysics Data System (ADS)

    Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

    2014-03-01

    Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

  1. Tissue temperature monitoring during interstitial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Svensson, Jenny; Johansson, Ann; Svanberg, Katarina; Andersson-Engels, Stefan

    2005-04-01

    During δ-aminolevulinic acid (ALA) based Interstitial Photodynamic Therapy (IPDT) a high light fluence rate is present close to the source fibers. This might induce an unintentional tissue temperature increase of importance for the treatment outcome. In a previous study, we have observed, that the absorption in the tissue increases during the treatment. A system to measure the local tissue temperature at the source fibers during IPDT on tissue phantoms is presented. The temperature was measured by acquiring the fluorescence from small Cr3+-doped crystals attached to the tip of the illumination fiber used in an IPDT-system. The fluorescence of the Alexandrite crystal used is temperature dependent. A ratio of the intensity of the fluorescence was formed between two different wavelength bands in the red region. The system was calibrated by immersing the fibers in an Intralipid solution placed in a temperature controlled oven. Measurements were then performed by placing the fibers interstitially in a pork chop as a tissue phantom. Measurements were also performed superficially on skin on a volunteer. A treatment was conducted for 10 minutes, and the fluorescence was measured each minute during the illumination. The fluorescence yielded the temperature at the fiber tip through the calibration curve. The measurements indicate a temperature increase of a few degrees during the simulated treatment.

  2. Novel Photodynamics in Phytochrome & Cyanobacteriochrome Photosensory Proteins

    NASA Astrophysics Data System (ADS)

    Larsen, Delmar

    2015-03-01

    The photodynamics of recently characterized phytochrome and cyanobacteriochrome photoreceptors are discussed. Phytochromes are red/far-red photosensory proteins that utilize the photoisomerization of a linear tetrapyrrole (bilin) chromophore to detect the red to far-red light ratio. Cyanobacteriochromes (CBCRs) are distantly related cyanobacterial photosensors with homologous bilin-binding GAF domains, but exhibit greater spectral diversity. The excited-state mechanisms underlying the initial photoisomerization in the forward reactions of the cyanobacterial photoreceptor Cph1 from Synechocystis, the RcaE CBCR from Fremyella diplosiphon, and Npr6012g4 CBCR from Nostoc punctiforme were contrasted via multipulse pump-dump-probe transient spectroscopy. A rich excited-state dynamics are resolved involving a complex interplay of excited-state proton transfer, photoisomerization, multilayered inhomogeneity, and reactive intermediates, and Le Chatelier redistribution. NpR6012g4 exhibits a high quantum yield for its forward photoreaction (40%) that was ascribed to the activity of hidden, productive ground-state intermediates via a ``second chance initiation dynamics'' (SCID) mechanism. This work was supported by a grant from the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, United States Department of Energy (DOE DE-FG02-09ER16117).

  3. 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.

  4. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  5. Photodynamic therapy using a protoporphyrinogen oxidase inhibitor.

    PubMed

    Fingar, V H; Wieman, T J; McMahon, K S; Haydon, P S; Halling, B P; Yuhas, D A; Winkelman, J W

    1997-10-15

    The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway. Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a protoporphyrinogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX. Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, the duration of inhibitor exposure to animals, and the amount of light used in PDT. Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis. Tumor cure in animals given 4000 ppm FP-846 in feed for 3 days and 300 J/cm2 602-670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%). PMID:9377568

  6. Photodynamic therapy on normal rabbit mandible

    NASA Astrophysics Data System (ADS)

    Fan, Kathleen F.; Hopper, Colin; Speight, Paul M.; Davies, Claire; Bown, Stephen G.

    1995-03-01

    Photodynamic therapy has been proposed as an intra-operative adjunct to surgical resection of tumors invading bone. To assess this, we studied the effects of PDT in normal bone. Forty- four rabbits were sensitized with Photofrin 3 mg/kg, 5-aminolaevulinic acid (ALA) 400 mg/kg, or meso-tetrahydroxyphenylchlorin (mTHPC) 0.3 mg/kg. A mandibular incisor was removed and the socket irradiated with a cylindrical diffusion fiber (630 nm Photofrin and ALA, 650 nm mTHPC, 100 J per treatment). Irradiation was given 1 or 48 hours after Photofrin, 72 hours after mTHPC, whilst 2 doses were given 2.5 and 4 hours after the first fractionated dose of ALA. The socket of the ipsilateral maxillary incisor was used as a nonirradiated control to assess healing without PDT. Other controls assessed healing after irradiation of unsensitized animals. Rabbits were killed 3, 10, and 21 days after treatment. Tooth socket healing appeared to be the same in all groups of animals with evidence of woven bone formation by 10 days. We conclude that PDT is unlikely to have any effect on healing in normal bone, which makes it suitable for treating tumors invading bone.

  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. 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.

  9. 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) ).

  10. Photodynamic therapy of cervical intraepithelial neoplasia using hexaminolevulinate and methylaminolevulinate

    NASA Astrophysics Data System (ADS)

    Soergel, Philipp; Staboulidou, Ismini; Hertel, Herrmann; Schippert, Cordula; Hillemanns, Peter

    2009-06-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer. Previous studies indicated that photodynamic therapy (PDT) represents an effective treatment modality in CIN. In 28 patients with CIN 1 - 3, 1 - 2 cycles of PDT were conducted using hexaminolevulinate (HAL) or methylaminolevulinate (MAL) and a special light delivery system. After 6 months, biopsies were obtained to assess response. The overall response rate for complete or partial response was 65%. Photodynamic therapy using new ALA esters is effective and may offer unique advantages in the therapy of CIN.

  11. Photodynamic Therapy: The Imminent Milieu For Treating Oral Lesions

    PubMed Central

    Mohanty, Neeta; Jalaluddin, MD; Kotina, Sreekanth; Routray, Samapika; Ingale, Yashwant

    2013-01-01

    Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry. PMID:23905154

  12. Suppression of cucurbit scab on cucumber leaves by photodynamic dyes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this study was to test the ability of the photodynamic dyes bengal rose, toluidine blue, and methylene blue, to protect systemically cucumber plants from cucurbit scab. At the stage of one true leaf, water or aqueous solutions of the dyes were applied to the leaf as droplets. When the se...

  13. Photochemical predictive analysis of photodynamic therapy in dermatology

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    Photodynamic Therapy is a recent treatment modality that allows malignant tissue destruction. The technique provides a localized effect and good cosmetic results. The application of Photodynamic Therapy is based on the inoculation of a photosensitizer and the posterior irradiation by an optical source. This radiation chemically activates the drug and provokes reactions that lead to tissue necrosis. Nowadays there are fixed clinical Photodynamic Therapy protocols that make use of a particular optical dose and photosensitizer amount. These parameters are independent of the patient and the lesion. In this work we present a Photodynamic Therapy model that tries to predict the effect of the treatment on the skin. First the results of a clinical study in the Dermatology Department of the Marqués de Valdecilla University Hospital are presented. The most common lesions and some unsuccessful cases are stated. The predictive model proposed is based on a 3D optical propagation of radiation by a Monte Carlo approach. Once the optical energy is obtained, a complex photochemical model is employed. This model takes into account the electronic transitions between molecular levels and particles concentrations. As the process of generation of photosensitizer is not homogeneous, the photosensitizer distribution is also taken into account. The optical power of the source, the exposition time and the optochemical characteristics of the tissue can be varied. This implies that these parameters could be adjusted to the particular pathology we are dealing with, so the unsuccessful cases could be better treated.

  14. Photodynamic Inactivation of Bacteria and Biofilms Using Cationic Bacteriochlorins

    NASA Astrophysics Data System (ADS)

    Meerovich, G. A.; Tiganova, I. G.; Makarova, E. A.; Meerovich, I. G.; Romanova Ju., M.; Tolordova, E. R.; Alekseeva, N. V.; Stepanova, T. V.; Yu, Koloskova; Luk'anets, E. A.; Krivospitskaya, N. V.; Sipailo, I. P.; Baikova, T. V.; Loschenov, V. B.; Gonchukov, S. A.

    2016-02-01

    This work is devoted to the study of two new synthetic bacteriochlorins with four and eight cationic substitutes as the photosensitizers in the photodynamic process. The spectral and antibacterial properties of these photosensitizers in saline solution were investigated. It is shown, that the aggregation ability decreases and the antibacterial efficiency grows as the cationic substitute number increases.

  15. Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma

    PubMed Central

    Qumseya, Bashar J.; David, Waseem

    2013-01-01

    This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting. PMID:23423151

  16. Hybrid photoactive fullerene derivative-ruboxyl nanostructures for photodynamic therapy.

    PubMed

    Kotelnikov, Alexander I; Rybkin, Alexander Yu; Khakina, Ekaterina A; Kornev, Alexey B; Barinov, Alexander V; Goryachev, Nikolay S; Ivanchikhina, Anastasiya V; Peregudov, Alexander S; Martynenko, Vyacheslav M; Troshin, Pavel A

    2013-07-14

    Here we report the investigation of photophysical properties and photodynamic action of two novel water soluble hybrid molecular structures based on [60]fullerene dyads bearing covalently attached residues of anthracycline antibiotic "ruboxyl". Molecular structures of the designed compounds were confirmed by IR and UV-VIS absorption spectroscopy, electrospray mass spectrometry (compound 5), and (1)H and (13)C NMR spectroscopy. Dynamic light scattering, steady-state and kinetic fluorimetry and UV-VIS absorption spectroscopy techniques were used to study the behavior of the synthesized hybrid molecular structures in aqueous solutions. Photodynamic activity of the compounds was evaluated by monitoring the O2(-) generation under visible light irradiation using the NBT test. It has been shown that the anthracycline chromophore (ruboxyl moiety possesses no photodynamic activity) behaves as an efficient photosensitizer for the fullerene core operating via the energy and/or the electron transfer pathways. The presented approach opens up wide opportunities for the design of various fullerene-based donor-acceptor systems with enhanced photodynamic properties potentially suitable for biomedicinal applications. PMID:23712714

  17. 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

  18. 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

  19. Important cellular targets for antimicrobial photodynamic therapy.

    PubMed

    Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

    2016-09-01

    The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets. PMID:27221289

  20. 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

  1. 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

  2. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-04-15

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  3. [Photodynamic therapy of superficial bladder tumors].

    PubMed

    Misaki, T; Hisazumi, H; Hirata, A; Kunimi, K; Yamamoto, H; Amano, T; Kumaki, O; Koshida, K; Nishino, A; Nakazima, K

    1986-12-01

    Photodynamic therapy (PDT), using hematoporphyrin derivative (HPD) and the red light (wavelength 630 nm) of an argon-dye laser as the source of excitation energy was performed on 46 patients with superficial bladder tumors. Two methods of laser irradiation, (1) focal PDT using a 400 micron quartz fiber through a cystourethroscope in 22 patients with superficial bladder tumors and (2) whole bladder wall total PDT using a motor-driven laser light scattering device in 24 patients with multifocal carcinoma in situ and/or dysplasia of bladder mucosa associated with multicentric concurrent superficial tumors, were used. The patients in (2) had been referred for total cystectomy, and 19 of these 24 patients had a history of several transurethral resections, hyperthermia and/or instillation therapy. HPD 2-4 mg/kg was i.v. injected 48 to 72 hours before PDT. Judging from the results of 60 protrusions treated by focal PDT, the light power should be 200 mW/cm2 for 5-10 minutes or more and the total light energy should be 100 J/cm2 or more in tumors up to 2 cm in size. With focal PDT, 4 of the 22 patients had no recurrence with the mean tumor free time of 20.8 months. In 6 of the 24 patients treated with total PDT using 10, 20 or 30 J/cm2 of light energy, there was no recurrence with a mean tumor-free time of 7.5 months and there was no significant relationship between the recurrence rate and total light energy used. PMID:3825831

  4. Photodynamic Therapy for Malignant Brain Tumors

    PubMed Central

    AKIMOTO, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women’s Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  5. How to reuse a one-time pad and other notes on authentication, encryption, and protection of quantum information

    SciTech Connect

    Oppenheim, Jonathan; Horodecki, Michal

    2005-10-15

    Quantum information is a valuable resource which can be encrypted in order to protect it. We consider the size of the one-time pad that is needed to protect quantum information in a number of cases. The situation is dramatically different from the classical case: we prove that one can recycle the one-time pad without compromising security. The protocol for recycling relies on detecting whether eavesdropping has occurred, and further relies on the fact that information contained in the encrypted quantum state cannot be fully accessed. We prove the security of recycling rates when authentication of quantum states is accepted, and when it is rejected. We note that recycling schemes respect a general law of cryptography which we introduce relating the size of private keys, sent qubits, and encrypted messages. We discuss applications for encryption of quantum information in light of the resources needed for teleportation. Potential uses include the protection of resources such as entanglement and the memory of quantum computers. We also introduce another application: encrypted secret sharing and find that one can even reuse the private key that is used to encrypt a classical message. In a number of cases, one finds that the amount of private key needed for authentication or protection is smaller than in the general case.

  6. 24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false One-time or up-front mortgage... INSURANCE Eligibility Requirements and Underwriting Procedures Eligible Mortgages § 203.18c One-time or up... amount of any mortgage may be increased by the amount of any one-time or up-front mortgage...

  7. 24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false One-time or up-front mortgage... INSURANCE Eligibility Requirements and Underwriting Procedures Eligible Mortgages § 203.18c One-time or up... amount of any mortgage may be increased by the amount of any one-time or up-front mortgage...

  8. 24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false One-time or up-front mortgage... INSURANCE Eligibility Requirements and Underwriting Procedures Eligible Mortgages § 203.18c One-time or up... amount of any mortgage may be increased by the amount of any one-time or up-front mortgage...

  9. 24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false One-time or up-front mortgage... INSURANCE Eligibility Requirements and Underwriting Procedures Eligible Mortgages § 203.18c One-time or up... amount of any mortgage may be increased by the amount of any one-time or up-front mortgage...

  10. Potentiation of thermal inactivation of glyceraldehyde-3-phosphate dehydrogenase by photodynamic treatment. A possible model for the synergistic interaction between photodynamic therapy and hyperthermia.

    PubMed Central

    Prinsze, C; Dubbelman, T M; Van Steveninck, J

    1991-01-01

    Thermal inactivation of glyceraldehyde-3-phosphate dehydrogenase appeared to be caused by a conformational mechanism, without involvement of covalent reactions. On the other hand, photodynamic inactivation of the enzyme (induced by illumination in the presence of Photofrin II) was caused by photo-oxidation of the essential thiol group in the active centre. A short photodynamic treatment of the enzyme, leading to only a limited inactivation, caused a pronounced potentiation of subsequent thermal inactivation, as measured over the temperature range 40-50 degrees C. Analysis of the experimental results according to the Arrhenius equation revealed that both the activation energy of thermal inactivation and the frequency factor (the proportionality constant) were significantly decreased by the preceding photodynamic treatment. The experimental results indicate a mechanism in which limited photodynamic treatment induced a conformational change of the protein molecule. This conformational change did not contribute to photodynamic enzyme inhibition, but was responsible for the decreased frequency factor and activation energy of subsequent thermal inactivation of the enzyme. The opposing effects of decreased activation energy and decreased frequency factor resulted in potentiation of thermal inactivation of the enzyme over the temperature range 40-50 degrees C. With other proteins, different results were obtained. With amylase the combined photodynamic and thermal effects were not synergistic, but additive, and photodynamic treatment had no effect on the frequency factor and the activation energy of thermal inactivation. With respect to myoglobin denaturation, the photodynamic and thermal effects were antagonistic over the whole practically applicable temperature range. Limited photodynamic treatment protected the protein against heat-induced precipitation, concomitantly increasing both the frequency factor and the activation energy of the process. These results offer a

  11. A study of the photodynamic effect on cancerous cells A study of the photodynamic effect on cancerous cells

    NASA Astrophysics Data System (ADS)

    AlSalhi, M. S.; Atif, M.; Alobiadi, A. A.; Aldwayyan, A. S.

    2012-08-01

    We use a rate equation model for the loss of the photosensitizer resulting from photo-oxidation (singlet oxygen attack on the photodynamic therapy (PDT) photosensitizer). It also incorporates the effect of photobleaching (photosensitizer decay) on the oxygen and the photosensitizer concentration which play an important role in photodynamic damage in different cell cultures. As a part of this study, we calculated photodynamic damage against the exposure time. Secondly photodynamic damage in different treated malignant/neoplastic as well as normal cell lines (Hep-2, A-549, and WI-38) has been investigated using a continuous wave (CW) He-Ne laser (633 nm of red wavelength). For determination of effectiveness of photodynamic damage two sorts of experiments are conducted. In first step of this experiment, given cell lines were photosensitized/treated with 1 ml of δ-aminolevulinic acid (ALA) having working solution of 200 μg/ml and after 4 hours of time of incubation ALA treated cells were exposed/irradiated with different doses (15 - 60 J/cm2) with constant irradiation time (15 minutes approximately). Same technique with exception of different concentration of ALA (60 - 800 μg/ml) and light dose (15 - 60 J/cm2/5-20 mW of power along with time of irradiation 15 minutes approximately) has been applied in second step of experiment. Finally result has been verified by using staining of mitochondria technique. 633 nm He-Ne (CW) along with 400 μg/ml of 5-ALA stipulates excellent therapeutic results verified by using mitochondrial staining technique as well as cell hemocytometry. Both the experimental as well as theoretical results are in good agreement with each other.

  12. Deterministic Secure Quantum Communication and Authentication Protocol based on Extended GHZ-W State and Quantum One-time Pad

    NASA Astrophysics Data System (ADS)

    Li, Na; Li, Jian; Li, Lei-Lei; Wang, Zheng; Wang, Tao

    2016-04-01

    A deterministic secure quantum communication and authentication protocol based on extended GHZ-W state and quantum one-time pad is proposed. In the protocol, state |φ -> is used as the carrier. One photon of |φ -> state is sent to Alice, and Alice obtains a random key by measuring photons with bases determined by ID. The information of bases is secret to others except Alice and Bob. Extended GHZ-W states are used as decoy photons, the positions of which in information sequence are encoded with identity string ID of the legal user, and the eavesdropping detection rate reaches 81%. The eavesdropping detection based on extended GHZ-W state combines with authentication and the secret ID ensures the security of the protocol.

  13. Information verification cryptosystem using one-time keys based on double random phase encoding and public-key cryptography

    NASA Astrophysics Data System (ADS)

    Zhao, Tieyu; Ran, Qiwen; Yuan, Lin; Chi, Yingying; Ma, Jing

    2016-08-01

    A novel image encryption system based on double random phase encoding (DRPE) and RSA public-key algorithm is proposed. The main characteristic of the system is that each encryption process produces a new decryption key (even for the same plaintext), thus the encryption system conforms to the feature of the one-time pad (OTP) cryptography. The other characteristic of the system is the use of fingerprint key. Only with the rightful authorization will the true decryption be obtained, otherwise the decryption will result in noisy images. So the proposed system can be used to determine whether the ciphertext is falsified by attackers. In addition, the system conforms to the basic agreement of asymmetric cryptosystem (ACS) due to the combination with the RSA public-key algorithm. The simulation results show that the encryption scheme has high robustness against the existing attacks.

  14. Deterministic Secure Quantum Communication and Authentication Protocol based on Extended GHZ-W State and Quantum One-time Pad

    NASA Astrophysics Data System (ADS)

    Li, Na; Li, Jian; Li, Lei-Lei; Wang, Zheng; Wang, Tao

    2016-08-01

    A deterministic secure quantum communication and authentication protocol based on extended GHZ-W state and quantum one-time pad is proposed. In the protocol, state | φ -> is used as the carrier. One photon of | φ -> state is sent to Alice, and Alice obtains a random key by measuring photons with bases determined by ID. The information of bases is secret to others except Alice and Bob. Extended GHZ-W states are used as decoy photons, the positions of which in information sequence are encoded with identity string ID of the legal user, and the eavesdropping detection rate reaches 81%. The eavesdropping detection based on extended GHZ-W state combines with authentication and the secret ID ensures the security of the protocol.

  15. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part three of a five-part series

    PubMed Central

    2008-01-01

    The use of aminolevulinic acid photodynamic therapy and methyl ester of aminolevulinic acid photodynamic therapy has become commonplace in dermatology for the treatment of actinic keratoses, among other clinical entities. An intriguing question that has arisen is whether we can utilize these medicines for a chemopreventive effect; that is, preventing or delaying the onset of actinic keratoses and perhaps nonmelanoma skin cancers. This manuscript reviews the current literature and anecdotal evidence that suggests that aminolevulinic acid photodynamic therapy and methyl ester of aminolevulinic acid photodynamic therapy may indeed be chemopreventive and thus useful in preventing and/or delaying these lesions. PMID:21212845

  16. Enhancement of selectivity for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bedwell, Joanne

    Photodynamic Therapy (PDT) is a technique for producing localised tissue damage with low power light following prior administration of a photosensitising drug. The promise of PDT has been based on the selective retention of photosensitisers by tumours, but this aspect has been over-emphasised with a maximum ratio of photosensitiser concentration of 3:1, tumour to normal, for extracranial tumours and current drugs. This makes selective tumour necrosis difficult to achieve. This thesis explores ways in which selectivity may be improved. Aluminium sulphonated phthalocyanine (AlSPc) has better photochemical properties than the widely used HpD and Photofrin II, but has the same tumour selectivity, although the ratio was improved marginally using its disulphonated component. However, when used in conjunction with the radioprotective drug W7, in a rat colon cancer model, tumour necrosis was the same as without W7 while there was no damage to adjacent normal colon. A radical new approach is to give 5-aminolaevulinic acid (ALA) which induces endogenous production of the photosensitiser protoporphyrin IX. This improves selectivity in the rat colon cancer to 6:1 (tumour to normal mucosa), but also sensitises the mucosa selectively compared with the underlying muscle (10:1), giving a tumour to muscle ratio of 60:1. This has enormous potential for treating small tumours or areas of dysplasia in a range of hollow organs. ALA also has the major advantages of a short optimum drug to light time (typically 4-6 hours), short duration of skin sensitivity (approximately 24 hours) and it can be given orally with minimal systemic toxicity. This work has also shown in vitro that PDT with AlSPc sensitisation can kill helicohacter pylori at doses unlikely to affect gastric mucosa. In conclusion, by careful choice of photosensitising agents and treatment regimes, it is possible to limit PDT effects to abnormal tissues, and even if there is some normal tissue damage, in most cases, this heals

  17. Trichocyanines: a Red-Hair-Inspired Modular Platform for Dye-Based One-Time-Pad Molecular Cryptography

    PubMed Central

    Leone, Loredana; Pezzella, Alessandro; Crescenzi, Orlando; Napolitano, Alessandra; Barone, Vincenzo; d’Ischia, Marco

    2015-01-01

    Current molecular cryptography (MoCryp) systems are almost exclusively based on DNA chemistry and reports of cryptography technologies based on other less complex chemical systems are lacking. We describe herein, as proof of concept, the prototype of the first asymmetric MoCryp system, based on an 8-compound set of a novel bioinspired class of cyanine-type dyes called trichocyanines. These novel acidichromic cyanine-type dyes inspired by red hair pigments were synthesized and characterized with the aid of density functional theory (DFT) calculations. Trichocyanines consist of a modular scaffold easily accessible via an expedient condensation of 3-phenyl- or 3-methyl-2H-1,4-benzothiazines with N-dimethyl- or o-methoxyhydroxy-substituted benzaldehyde or cinnamaldehyde derivatives. The eight representative members synthesized herein can be classified as belonging to two three-state systems tunable through four different control points. This versatile dye platform can generate an expandable palette of colors and appears to be specifically suited to implement an unprecedented single-use asymmetric molecular cryptography system. With this system, we intend to pioneer the translation of digital public-key cryptography into a chemical-coding one-time-pad-like system. PMID:26246999

  18. Cryptanalysis and improvement of quantum broadcast communication and authentication protocol with a quantum one-time pad

    NASA Astrophysics Data System (ADS)

    Liu, Zhi-Hao; Chen, Han-Wu

    2016-08-01

    The security of quantum broadcast communication (QBC) and authentication protocol based on Greenberger–Horne–Zeilinger (GHZ) state and quantum one-time pad is analyzed. It is shown that there are some security issues in this protocol. Firstly, an external eavesdropper can take the intercept–measure–resend attack strategy to eavesdrop on 0.369 bit of every bit of the identity string of each receiver without being detected. Meanwhile, 0.524 bit of every bit of the secret message can be eavesdropped on without being detected. Secondly, an inner receiver can take the intercept–measure–resend attack strategy to eavesdrop on half of the identity string of the other’s definitely without being checked. In addition, an alternative attack called the CNOT-operation attack is discussed. As for the multi-party QBC protocol, the attack efficiency increases with the increase of the number of users. Finally, the QBC protocol is improved to a secure one. Project supported by the National Natural Science Foundation of China (Grant Nos. 61502101 and 61170321), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK20140651), the Research Fund for the Doctoral Program of Higher Education, China (Grant No. 20110092110024), and the Project Funded by PAPD and CICAEET.

  19. Trichocyanines: a Red-Hair-Inspired Modular Platform for Dye-Based One-Time-Pad Molecular Cryptography.

    PubMed

    Leone, Loredana; Pezzella, Alessandro; Crescenzi, Orlando; Napolitano, Alessandra; Barone, Vincenzo; d'Ischia, Marco

    2015-06-01

    Current molecular cryptography (MoCryp) systems are almost exclusively based on DNA chemistry and reports of cryptography technologies based on other less complex chemical systems are lacking. We describe herein, as proof of concept, the prototype of the first asymmetric MoCryp system, based on an 8-compound set of a novel bioinspired class of cyanine-type dyes called trichocyanines. These novel acidichromic cyanine-type dyes inspired by red hair pigments were synthesized and characterized with the aid of density functional theory (DFT) calculations. Trichocyanines consist of a modular scaffold easily accessible via an expedient condensation of 3-phenyl- or 3-methyl-2H-1,4-benzothiazines with N-dimethyl- or o-methoxyhydroxy-substituted benzaldehyde or cinnamaldehyde derivatives. The eight representative members synthesized herein can be classified as belonging to two three-state systems tunable through four different control points. This versatile dye platform can generate an expandable palette of colors and appears to be specifically suited to implement an unprecedented single-use asymmetric molecular cryptography system. With this system, we intend to pioneer the translation of digital public-key cryptography into a chemical-coding one-time-pad-like system. PMID:26246999

  20. Towards image-guided photodynamic therapy of Glioblastoma

    NASA Astrophysics Data System (ADS)

    Mallidi, Srivalleesha; Huang, Huang-Chiao; Liu, Joyce; Mai, Zhiming; Hasan, Tayyaba

    2013-03-01

    Glioblastoma (GBM) is an aggressive cancer with dismal survival rates and few new treatment options. Fluorescence guided resection of GBM followed by photodynamic therapy (PDT) has shown promise in several chemo- or radiotherapy non-responsive GBM treatments clinically. PDT is an emerging light and photosensitizer (PS) mediated cytotoxic method. However, as with other therapeutic modalities, the outcomes are variable largely due to the nonpersonalization of dose parameters. The variability can be attributed to the differences in heterogeneous photosensitizer accumulation in tumors. Building upon our previous findings on utilizing PS fluorescence for designing tumor-specific PDT dose, we explore the use of photoacoustic imaging, a technique that provides contrast based on the tissue optical absorption properties, to obtain 3D information on the tumoral photosensitizer accumulation. The findings of this study will form the basis for customized photodynamic therapy for glioblastoma and have the potential to serve as a platform for treatment of other cancers.

  1. First experience of application of photodynamic therapy in keratoplasty

    NASA Astrophysics Data System (ADS)

    Fyodorov, Svyatoslav N.; Kopayeva, V. G.; Andreev, Yu. V.; Stranadko, Eugeny P.; Ponomariov, G. V.

    1996-12-01

    Vascular effect of photodynamic therapy has been studied in patients with corneal neovascularized transplant in 10 cases. THe injection of photoheme intravenously were made with subsequent irradiation by light of argon-pumped dye laser with light density of 150-300 mW/cm2 for 10-15 minutes. Energy density consisted 150-300 J/cm2. In all the cases at the time of irradiation the aggregated blood flow was appeared followed by blood flow stasis. In post- operative period the vessels disintegrated into separate fragments which disappeared completely after 10-15 days. Taking into account the data of light microscope, the disappearance of the vessels took place as a result of the vascular endothelium lysis along the vascular walls. The vessel alteration study presented in this paper, may also serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.

  2. Benzochloroporphyrin derivative photosensitizer-mediated photodynamic therapy for Ewing sarcoma.

    PubMed

    Sun, Mengxiong; Zhou, Chenghao; Zeng, Hui; Yin, Fei; Wang, Zhuoying; Yao, Jianzhong; Hua, Yingqi; Cai, Zhengdong

    2016-07-01

    In this study, we evaluated the photodynamic efficacy of a new photosensitizer, benzochloroporphyrin derivative 18 (BCPD-18), in Ewing sarcoma. We found that BCPD-18 decreased the viability of TC-71 cells irradiated by 670nm laser in a concentration dependent manner. We also observed cells undergoing apoptosis as well as cell cycle arrest at the G2M phase after BCPD-18-mediated photodynamic therapy (BCPD-PDT). In addition, in vivo study (subcutaneous and orthotopic models) showed that BCPD-PDT reduced tumor size, tumor weight and tumor-bearing leg weight. After PDT, apoptosis was shown in vivo. Bax expression was increased, and Bcl-2 expression was decreased. This study provides evidence that BCPD-18 could probably be a useful photosensitizer in PDT for Ewing sarcoma. PMID:27113445

  3. Targeted photodynamic therapy--a promising strategy of tumor treatment.

    PubMed

    Bugaj, Andrzej M

    2011-07-01

    Targeted therapy is a new promising therapeutic strategy, created to overcome growing problems of contemporary medicine, such as drug toxicity and drug resistance. An emerging modality of this approach is targeted photodynamic therapy (TPDT) with the main aim of improving delivery of photosensitizer to cancer tissue and at the same time enhancing specificity and efficiency of PDT. Depending on the mechanism of targeting, we can divide the strategies of TPDT into "passive", "active" and "activatable", where in the latter case the photosensitizer is activated only in the target tissue. In this review, contemporary strategies of TPDT are described, including new innovative concepts, such as targeting assisted by peptides and aptamers, multifunctional nanoplatforms with navigation by magnetic field or "photodynamic molecular beacons" activatable by enzymes and nucleic acid. The imperative of introducing a new paradigm of PDT, focused on the concepts of heterogeneity and dynamic state of tumor, is also called for. PMID:21547329

  4. Photoswitching of salicylidene methylamine: a theoretical photodynamics study.

    PubMed

    Spörkel, Lasse; Jankowska, Joanna; Thiel, Walter

    2015-02-12

    Photoswitching of simple photochromic molecules attracts substantial attention because of its possible role in future photon-driven molecular electronics. Here we model the full photoswitching cycle of a minimal photochromic Schiff base-salicylidene methylamine (SMA). We perform semiempirical nonadiabatic on-the-fly photodynamics simulations at the OM2/MRCI level and thoroughly analyze the structural time evolution and switching efficiency of the system. We also identify and examine in detail the crucial steps in the SMA photochemistry ruled by excited-state intramolecular proton transfer. The results place the investigated model aromatic Schiff base among the promising candidates for novel photoswitching molecular materials. Our study also shows the potential of the semiempirical multireference photodynamics simulations as a tool for early stage molecular photodevice design. PMID:25341075

  5. Latex carrier for improving protoporphyrin IX for photodynamic therapy.

    PubMed

    Bui, Brian; Liu, Li; Chen, Wei

    2016-06-01

    Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer. PMID:27020668

  6. Immune Response Following Photodynamic Therapy For Bladder Cancer

    NASA Astrophysics Data System (ADS)

    Raymond K.

    1989-06-01

    This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

  7. Photodynamic therapy: Promotion of efficacy by a sequential protocol

    PubMed Central

    Kessel, David

    2016-01-01

    Photodynamic therapy (PDT) offers a new approach to selective tumor eradication. Modifications designed to increase and optimize efficacy continue to emerge. Selective photodamage to malignant cells and their environment can bring about tumor cell destruction, shutdown of the tumor vasculature, stimulation of immunologic anti-tumor effects and potentiation of other therapeutic effects. Current development of combination protocols may provide a better rationale for integration of PDT into clinical practice. An example described here is the ability of a sequential (two-sensitizer) PDT protocol to enhance the efficacy of photokilling. The first step involves low-level lysosomal photodamage that has been shown to promote the apoptotic response to subsequent photodynamic effects directed at mitochondria. In this report, we demonstrate the ability of Photofrin, an FDA-approved photosensitizing agent, to serve as either the first or second element of the sequential protocol. PMID:27528795

  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. Use of Photosensitizers in Semisolid Formulations for Microbial Photodynamic Inactivation.

    PubMed

    González-Delgado, José A; Kennedy, Patrick J; Ferreira, Marta; Tomé, João P C; Sarmento, Bruno

    2016-05-26

    Semisolid formulations, such as gels, creams and ointments, have recently contributed to the progression of photodynamic therapy (PDT) and microbial photodynamic inactivation (PDI) in clinical applications. The most important challenges facing this field are the physicochemical properties of photosensitizers (PSs), optimal drug release profiles, and the photosensitivity of surrounding tissues. By further integration of nanotechnology with semisolid formulations, very promising pharmaceuticals have been generated against several dermatological diseases (PDT) and (antibiotic-resistant) pathogenic microorganisms (PDI). This review focuses on the different PSs and their associated semisolid formulations currently found in both the market and clinical trials that are used in PDT/PDI. Special emphasis is placed on the advantages that the semisolid formulations bring to drug delivery in PDI. Lastly, some potential considerations for improvement in this field are also discussed. PMID:26569024

  10. Photoswitching of Salicylidene Methylamine: A Theoretical Photodynamics Study

    PubMed Central

    2014-01-01

    Photoswitching of simple photochromic molecules attracts substantial attention because of its possible role in future photon-driven molecular electronics. Here we model the full photoswitching cycle of a minimal photochromic Schiff base–salicylidene methylamine (SMA). We perform semiempirical nonadiabatic on-the-fly photodynamics simulations at the OM2/MRCI level and thoroughly analyze the structural time evolution and switching efficiency of the system. We also identify and examine in detail the crucial steps in the SMA photochemistry ruled by excited-state intramolecular proton transfer. The results place the investigated model aromatic Schiff base among the promising candidates for novel photoswitching molecular materials. Our study also shows the potential of the semiempirical multireference photodynamics simulations as a tool for early stage molecular photodevice design. PMID:25341075

  11. The impact of absorbed photons on antimicrobial photodynamic efficacy.

    PubMed

    Cieplik, Fabian; Pummer, Andreas; Regensburger, Johannes; Hiller, Karl-Anton; Späth, Andreas; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

    2015-01-01

    Due to increasing resistance of pathogens toward standard antimicrobial procedures, alternative approaches that are capable of inactivating pathogens are necessary in support of regular modalities. In this instance, the photodynamic inactivation of bacteria (PIB) may be a promising alternative. For clinical application of PIB it is essential to ensure appropriate comparison of given photosensitizer (PS)-light source systems, which is complicated by distinct absorption and emission characteristics of given PS and their corresponding light sources, respectively. Consequently, in the present study two strategies for adjustment of irradiation parameters were evaluated: (i) matching energy doses applied by respective light sources (common practice) and (ii) by development and application of a formula for adjusting the numbers of photons absorbed by PS upon irradiation by their corresponding light sources. Since according to the photodynamic principle one PS molecule is excited by the absorption of one photon, this formula allows comparison of photodynamic efficacy of distinct PS per excited molecule. In light of this, the antimicrobial photodynamic efficacy of recently developed PS SAPYR was compared to that of clinical standard PS Methylene Blue (MB) regarding inactivation of monospecies biofilms formed by Enterococcus faecalis and Actinomyces naeslundii whereby evaluating both adjustment strategies. PIB with SAPYR exhibited CFU-reductions of 5.1 log10 and 6.5 log10 against E. faecalis and A. naeslundii, respectively, which is declared as a disinfectant efficacy. In contrast, the effect of PIB with MB was smaller when the applied energy dose was adjusted compared to SAPYR (CFU-reductions of 3.4 log10 and 4.2 log10 against E. faecalis and A. naeslundii), or there was even no effect at all when the number of absorbed photons was adjusted compared to SAPYR. Since adjusting the numbers of absorbed photons is the more precise and adequate method from a photophysical point

  12. The impact of absorbed photons on antimicrobial photodynamic efficacy

    PubMed Central

    Cieplik, Fabian; Pummer, Andreas; Regensburger, Johannes; Hiller, Karl-Anton; Späth, Andreas; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

    2015-01-01

    Due to increasing resistance of pathogens toward standard antimicrobial procedures, alternative approaches that are capable of inactivating pathogens are necessary in support of regular modalities. In this instance, the photodynamic inactivation of bacteria (PIB) may be a promising alternative. For clinical application of PIB it is essential to ensure appropriate comparison of given photosensitizer (PS)-light source systems, which is complicated by distinct absorption and emission characteristics of given PS and their corresponding light sources, respectively. Consequently, in the present study two strategies for adjustment of irradiation parameters were evaluated: (i) matching energy doses applied by respective light sources (common practice) and (ii) by development and application of a formula for adjusting the numbers of photons absorbed by PS upon irradiation by their corresponding light sources. Since according to the photodynamic principle one PS molecule is excited by the absorption of one photon, this formula allows comparison of photodynamic efficacy of distinct PS per excited molecule. In light of this, the antimicrobial photodynamic efficacy of recently developed PS SAPYR was compared to that of clinical standard PS Methylene Blue (MB) regarding inactivation of monospecies biofilms formed by Enterococcus faecalis and Actinomyces naeslundii whereby evaluating both adjustment strategies. PIB with SAPYR exhibited CFU-reductions of 5.1 log10 and 6.5 log10 against E. faecalis and A. naeslundii, respectively, which is declared as a disinfectant efficacy. In contrast, the effect of PIB with MB was smaller when the applied energy dose was adjusted compared to SAPYR (CFU-reductions of 3.4 log10 and 4.2 log10 against E. faecalis and A. naeslundii), or there was even no effect at all when the number of absorbed photons was adjusted compared to SAPYR. Since adjusting the numbers of absorbed photons is the more precise and adequate method from a photophysical point

  13. Photodynamic action on some pathogenic microorganisms of oral cavity

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, Ilya S.; Tuchin, Valery V.

    2001-10-01

    The work is devoted to an analysis of pre-clinical and clinical experiments on photodynamic action of HeNe laser radiation in aggregate with a cation thiazinium dye Methylene Blue (MB) on a mix of pathogenic and conditionally pathogenic aerobic bacteria being activators of pyoinflammatory diseases of oral cavity. Concentration of photosensitizes at which there is no own bactericidal influence on dying microflora, and parameters of influence at which the efficiency of irradiated microflora defeat reaches 99 % are determined.

  14. 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.

  15. Photodynamic Therapy Plus Chemotherapy Compared with Photodynamic Therapy Alone in Hilar Nonresectable Cholangiocarcinoma

    PubMed Central

    Wentrup, Robert; Winkelmann, Nicola; Mitroshkin, Andrey; Prager, Matthias; Voderholzer, Winfried; Schachschal, Guido; Jürgensen, Christian; Büning, Carsten

    2016-01-01

    Background/Aims Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. Methods We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. Results More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. Conclusions Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC. PMID:26814610

  16. Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

    PubMed Central

    de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

    2013-01-01

    The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this study we evaluated the combination of aPDT mediated by the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were exposed to light (590 nm) in the presence of hypericin (4µM), following electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E. coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we suggest that EP can potentiate the aPDT effect. PMID:24284122

  17. Nanotechnology-Based Photodynamic Therapy: Concepts, Advances, and Perspectives.

    PubMed

    Garg, Tarun; Jain, Nitin K; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    Photodynamic therapy (PDT) is a photoactive process that uses the combination of photosensitizers (PSs) and specific wavelengths of light for the treatment of solid tumors and other diseases. PDT received increased attention after regulatory approval of several photosensitizing drugs and light applicators worldwide. With the advent of newer PSs, the role of PDT in the treatment of cancer and other diseases has been revolutionized. In addition, various targeting strategies developed for site-specific delivery of PSs will be helpful for avoiding phototoxicity to normal tissues. Receptor-mediated targeted PDT approaches using nanocarriers offer the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. At present, clinical application of PDT is well established in medicine and surgery. Successfully used in dermatology, urology, gastroenterology, and neurosurgery, PDT has also seen much progress in basic sciences and clinical photodynamics in recent years. Currently, the use of PDT is just beginning, and more research must be performed to prove its therapeutic efficacy. However, nontoxic compounds involved in PDT provide a certain hope that it will evolve to be an effective mechanism for combating chronic diseases. PMID:26559433

  18. Synergistic antimicrobial effect of photodynamic therapy and ciprofloxacin.

    PubMed

    Ronqui, Maria Rita; de Aguiar Coletti, Tatiana Maria Starck Fogaça; de Freitas, Laura Marise; Miranda, Elaine Toscano; Fontana, Carla Raquel

    2016-05-01

    The occurrence of a variety of pathogens resistant to current antibiotics remains the major problem in medical care, especially when bacterial infections are established as biofilms. In this study, we propose the use of photodynamic therapy (PDT) as a monotherapy and associated with antibiotic as an alternative treatment. The aim of this study was to analyze the effects of PDT mediated by methylene blue (MB) on Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) in both biofilm and planktonic phases. Several concentrations of MB and light doses were tested. The bactericidal effects of PDT as a monotherapy did not increase with the concentration of photosensitizer, but were light dose-dependent. In addition, bacteria in biofilms were less affected than cells in the planktonic phase. Although not concentration-dependent, the disruption effect of PDT on biofilms was clearly illustrated by scanning electron microscopy (SEM). We also carried out experiments that evaluated the synergistic effect of photodynamic therapy and the antibiotic ciprofloxacin. The best results were obtained after combination treatment of photodynamic therapy followed by ciprofloxacin on biofilms, which increased bacterial reduction on biofilms, resulting in a 5.4 log reduction for S. aureus biofilm and approximately 7 log for E. coli biofilm. PMID:26971277

  19. Photodynamic therapy in the treatment of basal cell carcinoma

    PubMed Central

    Matei, C; Tampa, M; Poteca, T; Panea-Paunica, G; Georgescu, SR; Ion, RM; Popescu, SM; Giurcaneanu, C

    2013-01-01

    Photodynamic therapy (PDT) is a medical procedure based on the activation of the molecules of various exogenous or endogenous chemical substances called photosensitizers by a light source emitting radiation of an adequate wavelength, usually situated in the visible spectrum; photosensitizers are chemical compounds bearing the capacity to selectively concentrate in the neoplastic cells. The energy captured by the molecules of these substances pervaded in the tumor cells is subsequently discharged in the surrounding tissue, triggering certain photodynamic reactions that result in the destruction of the tumor. The procedure is applicable in numerous medical fields. Skin basal cell carcinoma (BCC), the most frequent type of cancer of the human species, is a cutaneous tumor that responds very well to this innovative treatment method. By reviewing numerous recent studies in the field, this article aims to present the role and the indications of photodynamic therapy in the management of basal cell carcinoma, as well as the most important results achieved so far by this therapy in the field of dermato-oncology. PMID:23599819

  20. 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.

  1. 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

  2. Dualities among one-time field theories with spin, emerging from a unifying two-time field theory

    SciTech Connect

    Bars, Itzhak; Quelin, Guillaume

    2008-06-15

    The relation between two-time physics (2T-physics) and the ordinary one-time formulation of physics (1T-physics) is similar to the relation between a 3-dimensional object moving in a room and its multiple shadows moving on walls when projected from different perspectives. The multiple shadows as seen by observers stuck on the wall are analogous to the effects of the 2T-universe as experienced in ordinary 1T spacetime. In this paper we develop some of the quantitative aspects of this 2T to 1T relationship in the context of field theory. We discuss 2T field theory in d+2 dimensions and its shadows in the form of 1T field theories when the theory contains Klein-Gordon, Dirac and Yang-Mills fields, such as the standard model of particles and forces. We show that the shadow 1T field theories must have hidden relations among themselves. These relations take the form of dualities and hidden spacetime symmetries. A subset of the shadows are 1T field theories in different gravitational backgrounds (different space-times) such as the flat Minkowski spacetime, the Robertson-Walker expanding universe, AdS{sub d-k}xS{sup k}, and others, including singular ones. We explicitly construct the duality transformations among this conformally flat subset, and build the generators of their hidden SO(d,2) symmetry. The existence of such hidden relations among 1T field theories, which can be tested by both theory and experiment in 1T-physics, is part of the evidence for the underlying d+2 dimensional spacetime and the unifying 2T-physics structure.

  3. Dualities among one-time field theories with spin, emerging from a unifying two-time field theory

    NASA Astrophysics Data System (ADS)

    Bars, Itzhak; Quélin, Guillaume

    2008-06-01

    The relation between two-time physics (2T-physics) and the ordinary one-time formulation of physics (1T-physics) is similar to the relation between a 3-dimensional object moving in a room and its multiple shadows moving on walls when projected from different perspectives. The multiple shadows as seen by observers stuck on the wall are analogous to the effects of the 2T-universe as experienced in ordinary 1T spacetime. In this paper we develop some of the quantitative aspects of this 2T to 1T relationship in the context of field theory. We discuss 2T field theory in d+2 dimensions and its shadows in the form of 1T field theories when the theory contains Klein-Gordon, Dirac and Yang-Mills fields, such as the standard model of particles and forces. We show that the shadow 1T field theories must have hidden relations among themselves. These relations take the form of dualities and hidden spacetime symmetries. A subset of the shadows are 1T field theories in different gravitational backgrounds (different space-times) such as the flat Minkowski spacetime, the Robertson-Walker expanding universe, AdSd-k×Sk, and others, including singular ones. We explicitly construct the duality transformations among this conformally flat subset, and build the generators of their hidden SO(d,2) symmetry. The existence of such hidden relations among 1T field theories, which can be tested by both theory and experiment in 1T-physics, is part of the evidence for the underlying d+2 dimensional spacetime and the unifying 2T-physics structure.

  4. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    NASA Astrophysics Data System (ADS)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  5. Studies of lipid peroxidation of rat blood after in vivo photodynamic treatment

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Yu.; Navolokin, Nikita A.; Nikitina, Victoria V.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Tuchin, Valery V.

    2011-10-01

    Lipid peroxidation (LP) of blood serum of laboratory animals after in vivo photodynamic treatment was investigated. To determine changes in LP the standard colorimetric test OXYSTAT was used. The results indicate an increase in the intensity of free radical generation in tissues induced by photodynamic treatment.

  6. Studies of lipid peroxidation of rat blood after in vivo photodynamic treatment

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Yu.; Navolokin, Nikita A.; Nikitina, Victoria V.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Tuchin, Valery V.

    2012-03-01

    Lipid peroxidation (LP) of blood serum of laboratory animals after in vivo photodynamic treatment was investigated. To determine changes in LP the standard colorimetric test OXYSTAT was used. The results indicate an increase in the intensity of free radical generation in tissues induced by photodynamic treatment.

  7. Towards dual photodynamic and antiangiogenic agents: design and synthesis of a phthalocyanine-chalcone conjugate.

    PubMed

    Tuncel, Sinem; Fournier-dit-Chabert, Jérémie; Albrieux, Florian; Ahsen, Vefa; Ducki, Sylvie; Dumoulin, Fabienne

    2012-02-14

    A phthalocyanine-chalcone conjugate has been designed to combine the vascular disrupting effect of chalcones with the photodynamic effect of phthalocyanines. This potential dual photodynamic and antiangiogenic agent was obtained by the condensation of a tetrahydroxylated non-peripherally substituted Zn(ii) phthalocyanine with an amino chalcone converted into the corresponding activated isocyanate. The conjugate was fully characterized. PMID:22215066

  8. [The randomized study of efficiency of preoperative photodynamic].

    PubMed

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Gerasin, A V; Kazakov, N V; Urtenova, M A; Chistiakov, I V

    2013-01-01

    The authors made a prospective randomized comparison of results of preoperative photodynamic therapy (PhT) with chemotherapy, preoperative chemotherapy in initial unresectable central non-small cell lung cancer in stage III. The efficiency and safety of preoperative therapy were estimated as well as the possibility of subsequent surgical treatment. The research included patients in stage IIIA and IIIB of central non-small cell lung cancer with lesions of primary bronchi and lower section of the trachea, which initially were unresectable, but potentially the patients could be operated on after preoperative treatment. The photodynamic therapy was performed using chlorine E6 and the light of wave length 662 nm. Since January 2008 till December 2011,42 patients were included in the research, 21 patients were randomized in the group for photodynamic therapy and 21--in group without PhT. These groups were compared according to their sex, age, stage of the disease and histological findings. After nonadjuvant treatment the remissions were reached in 19 (90%) patients of the group with PhT and in 16 (76%) patients without PhT and all the patients were operated on. The explorative operations were made on 3 patients out of 16 operated on in the group without PhT (19%). In the group PhT 14 pneumonectomies and 5 lobectomies were perfomed opposite 10 pneumonectomies and 3 lobectomies in group without PhT. The degree of radicalism of resection appears to be reliably higher in the group PhT (RO-89%, R1-11% as against RO-54%, R1-46% in group without PhT), p = 0.038. The preoperative endobronchial PhT conducted with chemotherapy was characterized by efficiency and safety, allowed the surgical treatment and elevated the degree of radicalism of this treatment in selected patients, initially assessed as unresectable. PMID:23808222

  9. Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica.

    PubMed

    Al-Qahtani, Ahmed; Alkahtani, Saad; Kolli, Bala; Tripathi, Pankaj; Dutta, Sujoy; Al-Kahtane, Abdullah A; Jiang, Xiong-Jie; Ng, Dennis K P; Chang, Kwang Poo

    2016-04-01

    Photodynamic inactivation ofLeishmaniaspp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency againstLeishmania tropicapromastigotes and axenic amastigotesin vitro The uptake of these PCs by bothLeishmaniastages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation ofLeishmaniaspp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitizedLeishmania tropicastrains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm(-2) Quantitative fluorescence assays based on the loss of GFP/CFSE from liveLeishmania tropicashowed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay.Leishmania tropicastrains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation ofLeishmaniaspp. for use as vaccines or vaccine carriers. PMID:26824938

  10. Preclinical studies of photodynamic therapy of intracranial tissues

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Sepers, Marja; Park, Jane; O'Carroll, Cindy; Pournazari, Poupak; Prosper, Joe; Wilson, Brian C.

    1997-05-01

    The applicability and limitations of the photodynamic threshold model were investigated for an intracranial tumor (VX2) and normal brain tissues in a rabbit model. Photodynamic threshold values for four different photosensitizers, i.e., Photofrin, 5(delta) -aminolaevulinic acid (5(delta) -ALA) induced Protoporphyrin IX (PPIX), Tin Ethyl Etiopurpurin (SnET2), and chloroaluminum phthalocyanine (AlClPc), were determined based on measured light fluence distributions, macroscopic photosensitizer concentration in various brain structures, and histologically determined extent of tissue necrosis following PDT. For Photofrin, AlClPc, and SnET2, normal brain displayed a significantly lower threshold value than VX2 tumor. For 5(delta) -ALA induced PPIX and SnET2 no or very little white matter damage, equalling to very high or infinite threshold values, was observed. Additionally, the latter two photosensitizers showed significantly lower uptake in white matter compared to other brain structures and VX2 tumor. Normal brain structures lacking a blood- brain-barrier, such as the choroid plexus and the meninges, showed high photosensitizer uptake for all photosensitizers, and, hence, are at risk when exposed to light. Results to date suggest that the photodynamic threshold values iares valid for white matter, cortex and VX2 tumor. For clinical PDT of intracranial neoplasms 5(delta) -ALA induced PPIX and SnET2 appear to be the most promising for selective tumor necrosis.However, the photosensitizer concentration in each normal brain structure and the fluence distribution throughout the treatment volume and adjacent tissues at risk must be monitored to maximize the selectivity of PDT for intracranial tumors.

  11. Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

    PubMed Central

    Walther, Jan; Schastak, Stanislas; Dukic-Stefanovic, Sladjana; Wiedemann, Peter; Neuhaus, Jochen; Claudepierre, Thomas

    2014-01-01

    Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma. PMID:24498108

  12. Efficient photodynamic therapy on human retinoblastoma cell lines.

    PubMed

    Walther, Jan; Schastak, Stanislas; Dukic-Stefanovic, Sladjana; Wiedemann, Peter; Neuhaus, Jochen; Claudepierre, Thomas

    2014-01-01

    Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma. PMID:24498108

  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. Three-dimensional illumination procedure for photodynamic therapy of dermatology

    NASA Astrophysics Data System (ADS)

    Hu, Xiao-ming; Zhang, Feng-juan; Dong, Fei; Zhou, Ya

    2014-09-01

    Light dosimetry is an important parameter that affects the efficacy of photodynamic therapy (PDT). However, the irregular morphologies of lesions complicate lesion segmentation and light irradiance adjustment. Therefore, this study developed an illumination demo system comprising a camera, a digital projector, and a computing unit to solve these problems. A three-dimensional model of a lesion was reconstructed using the developed system. Hierarchical segmentation was achieved with the superpixel algorithm. The expected light dosimetry on the targeted lesion was achieved with the proposed illumination procedure. Accurate control and optimization of light delivery can improve the efficacy of PDT.

  15. Reversible Photodynamic Chloride-Selective Sensor Based on Photochromic Spiropyran

    PubMed Central

    2012-01-01

    We report here for the first time on a reversible photodynamic bulk optode sensor based on the photoswitching of a spiropyran derivative (Sp). The photoswitching of Sp induces a large basicity increase in the polymeric phase, which triggers the extraction of Cl– and H+. Cl– is stabilized by a lipophilic chloride-selective ionophore inside the membrane, while H+ binds with the open form of Sp and induces a spectral change, hence providing the sensor signal. The system was studied with spectroscopic and electrochemical methods. PMID:23036043

  16. Intraoperative photodynamic therapy in laryngeal part of pharynx cancers

    NASA Astrophysics Data System (ADS)

    Loukatch, Erwin V.; Trojan, Vasily; Loukatch, Vjacheslav

    1996-12-01

    In clinic intraoperative photodynamic therapy (IPT) was done in patients with primal squamous cells cancer of the laryngeal part of the pharynx. The He-Ne laser and methylene blue as a photosensibilizator were used. Cobalt therapy in the postoperative period was done in dose 45 Gr. Patients of control groups (1-th group) with only laser and (2-th group) only methylene blue were controlled during three years with the main group. The statistics show certain differences of recidives in the main group compared to the control groups. These facts are allowing us to recommend the use of IPT as an additional method in ENT-oncology diseases treatment.

  17. Optical dosimetry in photodynamic therapy of human uterus and brain

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Svaasand, Lars O.; Hirschberg, Henry; Tadir, Yona; Tromberg, Bruce J.

    1999-06-01

    Optical 'dose' is one of the fundamental parameters required in the design of an efficacious regimen of photodynamic therapy (PDT). The issues involved in delivering a sufficient optical dose to the human uterus and brain during PDT will be discussed. Specifically, measurements of optical properties and fluence rates in excised human uteri are presented. Measured fluence rates are compared to the predictions of a simple diffusion model and the clinical utility of the treatment is discussed. The delivery of light to brain tissue via a surgically implanted balloon applicator will also be considered. The time required to deliver and adequate dose is calculated based on known optical properties and diffusion theory.

  18. On molecular mechanism of the photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Tretjakov, S. A.

    1995-01-01

    In this work we present the experimental results indicating that the photodestruction (inactivation) of glycolysis enzymes located in mitochondria and responsible for the energy providing of malignant tumors, could serve as a possible molecular mechanism of a photodynamic therapy of cancer. The formation of complexes between the glycolysis enzymes and sensitizer favors can lead to an effective photodestruction of the former [in the experiments lactate dehydrogenase (LDH), pyruvate kinase (PK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and water-soluble tetra(carboxiphenyl)porphyrine [T(CP)P] (the analogue of coprorphyrin) were used as photosensitizer.

  19. Fluorescent Molecular Imaging and Dosimetry Tools in Photodynamic Therapy

    PubMed Central

    Pogue, Brian W.; Samkoe, Kimberley S.; Gibbs-Strauss, Summer L.; Davis, Scott C.

    2013-01-01

    Measurement of fluorescence and phosphorescence in vivo is readily used to quantify the concentration of specific species that are relevant to photodynamic therapy. However, the tools to make the data quantitatively accurate vary considerably between different applications. Sampling of the signal can be done with point samples, such as specialized fiber probes or from bulk regions with either imaging or sampling, and then in broad region image-guided manner. Each of these methods is described below, the application to imaging photosensitizer uptake is discussed, and developing methods to image molecular responses to therapy are outlined. PMID:20552350

  20. HpD Photobiology And Photodynamic Therapy Of Bladder Carcinoma

    NASA Astrophysics Data System (ADS)

    Lin, Chi-Wei

    1988-02-01

    Bladder carcinoma is considered one of the most favorable targets for the application of photodynamic therapy (PDT) due to the accessibility of the bladder for light delivery. Examination of the bladder and surgical procedures are routinely performed by the insertion of an optical instrument called cystoscope through the urethra. Thus, the treatment of bladder cancer by PDT can be conducted through the cystoscope with minimal invasion. However, to achieve optimal results from this treatment, one must consider both the structure of the bladder and the nature of the carcinoma.

  1. Biomodulatory Approaches to Photodynamic Therapy for Solid Tumors

    PubMed Central

    Anand, Sanjay; Ortel, Bernhard J.; Pereira, Stephen P.; Hasan, Tayyaba; Maytin, Edward V.

    2012-01-01

    Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT versus surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed. PMID:22842096

  2. Destructive fat tissue engineering using photodynamic and selective photothermal effects

    NASA Astrophysics Data System (ADS)

    Tuchin, Valery V.; Yanina, Irina Yu.; Simonenko, Georgy V.

    2009-02-01

    Destructive fat tissue engineering could be realized using the optical method, which provides reduction of regional or site-specific accumulations of subcutaneous adipose tissue on the cell level. We hypothesize that light irradiation due to photodynamic and selective photothermal effects may lead to fat cell lypolytic activity (the enhancement of lipolysis of cell triglycerides due to expression of lipase activity and cell release of free fat acids (FFAs) due to temporal cell membrane porosity), and cell delayed killing due to apoptosis caused by the induced fat cell stress and/or limited cell necrosis.

  3. 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.

  4. Photodynamic therapy with laser scanning mode of tumor irradiation

    NASA Astrophysics Data System (ADS)

    Chepurna, Oksana; Shton, Irina; Kholin, Vladimir; Voytsehovich, Valerii; Popov, Viacheslav; Pavlov, Sergii; Gamaleia, Nikolai; Wójcik, Waldemar; Zhassandykyzy, Maral

    2015-12-01

    In this study we propose a new version of photodynamic therapy performed by laser scanning. The method consists in tumor treatment by a light beam of a small cross section which incrementally moves through the chosen area with a defined delay at each point and repetitively re-scans a zone starting from the initial position. Experimental evaluation of the method in vitro on murine tumor model showed that despite the dose, applied by scanning irradiation mode, was 400 times lower, the tumor inhibition rate conceded to attained with continuous irradiation mode by only 20%.

  5. Uniform irradiation of irregularly shaped cavities for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rem, Alex I.; van Gemert, Martin J. C.; van der Meulen, Freerk W.; Gijsbers, Geert H. M.; Beek, Johan F.

    1997-03-01

    It is difficult to achieve a uniform light distribution in irregularly shaped cavities. We have conducted a study on the use of hollow `integrating' moulds for more uniform light delivery of photodynamic therapy in irregularly shaped cavities such as the oral cavity. Simple geometries such as a cubical box, a sphere, a cylinder and a `bottle-neck' geometry have been investigated experimentally and the results have been compared with computed light distributions obtained using the `radiosity method'. A high reflection coefficient of the mould and the best uniform direct irradiance possible on the inside of the mould were found to be important determinants for achieving a uniform light distribution.

  6. 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

  7. Uniform irradiation of irregularly shaped cavities for photodynamic therapy.

    PubMed

    Rem, A I; van Gemert, M J; van der Meulen, F W; Gijsbers, G H; Beek, J F

    1997-03-01

    It is difficult to achieve a uniform light distribution in irregularly shaped cavities. We have conducted a study on the use of hollow 'integrating' moulds for more uniform light delivery of photodynamic therapy in irregularly shaped cavities such as the oral cavity. Simple geometries such as a cubical box, a sphere, a cylinder and a 'bottle-neck' geometry have been investigated experimentally and the results have been compared with computed light distributions obtained using the 'radiosity method'. A high reflection coefficient of the mould and the best uniform direct irradiance possible on the inside of the mould were found to be important determinants for achieving a uniform light distribution. PMID:9080537

  8. Study of photodynamic therapy in skin cancers and precancerous lesions

    NASA Astrophysics Data System (ADS)

    Wang, Jiabi; Gao, Menglin; Wen, Shijun; Wang, Mianjing

    1993-03-01

    Hematoporphyrin photodynamic therapy (HpD-PDT) was used to treat 50 patients (51 lesions) with skin cancers or precancerous lesions. The preliminary results were satisfactory, with 44 cases (45 lesions) obtaining excellent results, 4 cases good, 1 case fair, and 1 case poor. The effective rate was 98%, the significant remission rate 96%, and the complete remission rate 88.2%. Exposure to sunlight should be avoided after HpD injection, since it produces photosensitivity. A follow-up for 1 to 3 years confirmed that HpD-PDT is a good new adjuvant therapy for selected cases. It brings a hopeful future to the treatment of skin cancers.

  9. Two-photon photodynamic properties of TBO-AuNR-in-shell nanoparticles (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-Han; Yeh, Chen-Sheng; Cheng, Fong-Yu; Tsai, Zen-Uong; Liu, Tzu-Ming

    2016-03-01

    Photodynamic therapy (PDT) is a light-activated chemotherapeutic treatment that utilizes singlet oxygen and reactive oxygen species induced oxidative reactions to react with surrounding biological substrates, which either kills or irreversibly damages malignant cells. We used multiphoton nonlinear optical microscopy to observe the photo-dynamic effects of TBO-AuNR-in-shell NPs. Excited by femtosecond Cr:forsterite laser operating at 1230nm, singlet oxygen were generated through a plasmon-enhanced two-photon nonlinear optical process. For cells took up NPs, this photodynamic effect can kill the cell. From nonlinear optical microscopy images, we found they shrunk after 3 minutes of illumination.

  10. Encapsulation of methylene blue in polyacrylamide nanoparticle platforms protects its photodynamic effectiveness.

    PubMed

    Tang, Wei; Xu, Hao; Park, Edwin J; Philbert, Martin A; Kopelman, Raoul

    2008-05-01

    The ability to prevent methylene blue (MB), a photosensitizer, from being reduced by plasma reductases will greatly improve its efficacy in photodynamic therapy (PDT) applications. We have developed a delivery approach for PDT by encapsulating MB using nanoparticle platforms (NPs). The 30-nm polyacrylamide-based NPs provide protection for the embedded MB against reduction by diaphorase enzymes. Furthermore, our data shows the matrix-protected MB efficiently induces photodynamic damage to tumor cells. The unprecedented results demonstrate the significant in vitro photodynamic effectiveness of MB when encapsulated within NPs, which promises to open new opportunities for MB in its in vivo and clinical studies. PMID:18298950

  11. Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Modi, Nayan; Wilson, Brian C.

    2004-10-01

    The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as unlike apoptosis, necrotic cell death often leads to inflammation with increased intracranial pressure. The ability, therefore, to 'fine tune' PDT in favour of apoptosis is paramount. We have studied both acute (one time treatment) PDT (aPDT) and mPDT delivery strategies in combination with nicotinamide (NA) in an attempt to maximize the number of tumor cells dieing by apoptosis. Using several different glioma cell lines (9L, U87-MG and CNS-1) we now confirm that NA provides a dose-dependent (0.1-0.5 mM) increase in apoptotic cells following d-aminolevulinic acid-mediated aPDT or mPDT. Furthermore, using the 9L cell line stably transfected with the luciferase gene, NA was shown to delay the depletion of bioluminscence signal in aPDT and mPDT treated cells, inferring that adenosine triphosphate levels are maintained for longer following NA treatment. NA has previously been reported as promoting neuronal and vascular cell survival in normal brain following a number of neurological insults in which reactive oxygen species are implicated including, stroke, Alzheimer's disease and toxin-induced lesions. It is likely that the effects of NA reflect its capacity as an antioxidant as well as its ability to inhibit poly (adenosine diphosphate-ribose) polymerase-mediated depletion of ATP. Our results indicate that NA may prove therapeutically advantageous when used in combination with PDT treatment of brain tumors.

  12. 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.

  13. Direct phosphorescent detection of primary event of photodynamic action

    NASA Astrophysics Data System (ADS)

    Losev, Anatoly P.; Knukshto, Valentin N.; Zhuravkin, Ivan N.

    1994-07-01

    Highly phosphorescent photosensitizer Pd-tetra (o-methoxy-p-sulfo) phenyl porphyrin (Pd-MSPP) was used to follow the primary events of photodynamic action - quenching of triplet states by free oxygen in different systems: water solutions of proteins, cells and tissues in vivo and in vitro. The photosensitizer forms complexes with proteins in solutions and biosystems showing remarkable hypsochromic shifts of band and an increase of the quantum yield and lifetime of phosphorescence at the binding to proteins. In absence of oxygen the lifetime of phosphorescence is almost single exponential, and depends on the energy of lowest triplet state of the sensitizer. The photochemical quenching of the triplets by cell components is negligible. In presence of free oxygen the quenching of the sensitizer triplets takes place. The emission spectrum of singlet oxygen with maximum 1271 nm was recorded in water protein solutions and quantum yield of sensitized luminescence was measured. In the systems studied, oxygen consumption was detected and oxygen concentration was estimated in the course of photodynamics by an increase in photosensitizer phosphorescence lifetime, using laser flash photolysis technique. At least two exponential kinetics of the phosphorescence decay shows that the distribution of the free oxygen is not uniform in tissues.

  14. Hydrogels containing porphyrin-loaded nanoparticles for topical photodynamic applications.

    PubMed

    González-Delgado, José A; Castro, Pedro M; Machado, Alexandra; Araújo, Francisca; Rodrigues, Francisca; Korsak, Bárbara; Ferreira, Marta; Tomé, João P C; Sarmento, Bruno

    2016-08-20

    5,10,15,20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra-iodide (TMPyP), a potent water-soluble photosensitizer (PS) used in antimicrobial applications, was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TMPyP-PLGA) for topical delivery purposes. Nanoparticles resulted in a mean particle size around 130nm, narrow polydispersity index (PdI), spherical morphology and association efficiency up to 93%. Free TMPyP and TMPyP-PLGA nanoparticles were incorporated into Carbopol(®) hydrogels, resulting in controlled TMPyP release of about 60% and 20% after 4.5h, respectively. Critical properties such as appearance, clarity, viscosity and pH were maintained over time, as hydrogels were stable during 6 months at 4°C, 25°C/60% RH and 40°C/75% RH. For photodynamic applications, the photoproduction of singlet oxygen from these hydrogels was quite efficient being both formulations very photostable after 20min. No TMPyP permeation through pig ear skin was observed after 24h, and histological assays did not show relevant damages in surrounding tissues. All these excellent characteristics make them promising platforms for photodynamic applications through topical clinical use. PMID:27321129

  15. Free radical production in photodynamically inactivated cells of Rhodotorula glutinis.

    PubMed

    Maxwell, W A; Chichester, C O

    1970-01-01

    In an investigation of die-off of micro-organisms irradiated with high-intensity light, as might be expected in a space environment, the yeast Rhodotorula glutinis was used as a prototype. Previous results have shown that the yeast Rhodotorula glutinis can be photodynamically inactivated by laser radiation and by other intense light sources such as a xenon arc lamp. Experiments were conducted to determine if free radicals were involved in the inactivation of Rhodotorula glutinis when irradiated with light of wavelengths 300 nm and longer. Presumptive evidence that free radicals were involved in the photodynamic inactivation of the cells was found when it was shown that compounds capable of trapping free radicals were able to provide some protection to the cells. Further presumptive evidence that free radicals are involved was provided when it was shown that lipid peroxidation, which can be mediated by free radicals, is caused when the cells are irradiated. The actual production of free radicals was demonstrated by the detection of the presence of unpaired electron paramagnetic resonance spectra. These studies were conducted at both -30 degrees C and -160 degrees C. It was found that free radicals were produced at both temperatures and that cysteine could decrease the free radical population at -30 degrees C but not at -160 degrees C. PMID:11826893

  16. Treatment of spontaneously occurring veterinary tumors with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Legendre, Alfred; Sneed, Rick E.; Overholt, Bergein F.

    1992-06-01

    Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.

  17. 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

  18. Photodynamic research at Baylor University Medical Center Dallas, Texas

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.; Matthews, James Lester; Sogandares-Bernal, Franklin M.; Aronoff, Billie L.; Judy, Millard M.

    1993-03-01

    We received our first CO2 laser at Baylor University Medical Center in December 1974, following a trip to Israel in January of that year. Discussion with the customs office of the propriety of charging an 18% import tax lasted for nine months. We lost that argument. Baylor has been using lasers of many types for many procedures since that time. About ten years ago, through the kindness of Tom Dougherty and Roswell Park, we started working with photodynamic therapy, first with hematoporphyrin I and later with dihematoporphyrin ether (II). In February 1984, we were invited to a conference at Los Alamos, New Mexico, U.S.A. on medical applications of the free electron laser as part of the Star Wars Program. A grant application from Baylor was approved that November, but funding did not start for many months. This funding contributed to the development of a new research center as part of Baylor Research Institute. Many of the projects investigated at Baylor dealt with applications of the free electron laser (FEL), after it became available. A staff was assembled and many projects are still ongoing. I would like to outline those which are in some way related to photodynamic therapy.

  19. Photodynamic inactivation of contaminated blood with Staphylococcus aureus

    NASA Astrophysics Data System (ADS)

    Corrêa, Thaila Q.; Inada, Natalia M.; Pratavieira, Sebastião.; Blanco, Kate C.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-03-01

    The presence of bacteria in the bloodstream can trigger a serious systemic inflammation and lead to sepsis that cause septic shock and death. Studies have shown an increase in the incidence of sepsis over the years and it is mainly due to the increased resistance of microorganisms to antibiotics, since these drugs are still sold and used improperly. The bacterial contamination of blood is also a risk to blood transfusions. Thus, bacteria inactivation in blood is being studied in order to increase the security of the blood supply. The purpose of this study was to decontaminate the blood using the photodynamic inactivation (PDI). Human blood samples in the presence of Photogem® were illuminated at an intensity of 30 mW/cm2, and light doses of 10 and 15 J/cm2. Blood counts were carried out for the quantitative evaluation and blood smears were prepared for qualitative and morphological evaluation by microscopy. The results showed normal viability values for the blood cells analyzed. The light doses showed minimal morphological changes in the membrane of red blood cells, but the irradiation in the presence of the photosensitizer caused hemolysis in red blood cells at the higher concentrations of the photosensitizer. Experiments with Staphylococcus aureus, one of the responsible of sepsis, showed 7 logs10 of photodynamic inactivation with 50 μg/mL and 15 J/cm2 and 1 log10 of this microorganism in a co-culture with blood.

  20. Merocyanine-540 mediated photodynamic effects on Staphylococcus epidermidis biofilms

    NASA Astrophysics Data System (ADS)

    Sbarra, Maria Sonia; Di Poto, Antonella; Saino, Enrica; Visai, Livia; Minzioni, Paolo; Bragheri, Francesca; Cristiani, Ilaria

    2009-07-01

    Staphylococci are important causes of nosocomial and medical-device-related infections. Their virulence is attributed to the elaboration of biofilms that protect the organisms from immune system clearance and to increased resistance to phagocytosis and antibiotics. Photodynamic treatment (PDT) has been proposed as an alternative approach for the inactivation of bacteria in biofilms. In this study, we evaluated the antimicrobial activity of merocyanine 540 (MC 540), a photosensitizing dye that is used for purging malignant cells from autologous bone marrow grafts, against Staphylococcus epidermidis biofilms. We evaluated the effect of the combined photodynamic action of MC 540 and 532 nm laser on the viability and structure of biofilms of two Staphylococcus epidermidis strains. Significant inactivation of cells was observed in the biofilms treated with MC-540 and then exposed to laser radiation. Furthermore we found that the PDT effect, on both types of cells, was significantly dependent on both the light-dose and on the impinging lightintensity. Disruption of PDT-treated biofilm was confirmed by scanning electron microscopy (SEM).

  1. Evaluation of photodynamic therapy in adhesion protein expression

    PubMed Central

    PACHECO-SOARES, CRISTINA; MAFTOU-COSTA, MAIRA; DA CUNHA MENEZES COSTA, CAROLINA GENÚNCIO; DE SIQUEIRA SILVA, ANDREZA CRISTINA; MORAES, KAREN C.M.

    2014-01-01

    Photodynamic therapy (PDT) is a treatment modality that has clinical applications in both non-neoplastic and neoplastic diseases. PDT involves a light-sensitive compound (photosensitizer), light and molecular oxygen. This procedure may lead to several different cellular responses, including cell death. Alterations in the attachment of cancer cells to the substratum and to each other are important consequences of photodynamic treatment. PDT may lead to changes in the expression of cellular adhesion structure and cytoskeleton integrity, which are key factors in decreasing tumor metastatic potential. HEp-2 cells were photosensitized with aluminum phthalocyanine tetrasulfonate and zinc phthalocyanine, and the proteins β1-integrin and focal adhesion kinase (FAK) were assayed using fluorescence microscopy. The verification of expression changes in the genes for FAK and β1 integrin were performed by reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that HEp-2 cells do not express β-integrin or FAK 12 h following PDT. It was concluded that the PDT reduces the adhesive ability of HEp-2 cells, inhibiting their metastatic potential. The present study aimed to analyze the changes in the expression and organization of cellular adhesion elements and the subsequent metastatic potential of HEp-2 cells following PDT treatment. PMID:25013490

  2. ALA-Butyrate prodrugs for Photo-Dynamic Therapy

    NASA Astrophysics Data System (ADS)

    Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

    2010-05-01

    The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

  3. 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.

  4. Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer.

    PubMed

    Takehara, Kiyoto; Tazawa, Hiroshi; Okada, Naohiro; Hashimoto, Yuuri; Kikuchi, Satoru; Kuroda, Shinji; Kishimoto, Hiroyuki; Shirakawa, Yasuhiro; Narii, Nobuhiro; Mizuguchi, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

    2016-01-01

    Photodynamic therapy (PDT) is a minimally invasive antitumor therapy that eradicates tumor cells through a photosensitizer-mediated cytotoxic effect upon light irradiation. However, systemic administration of photosensitizer often makes it difficult to avoid a photosensitive adverse effect. The red fluorescent protein KillerRed generates reactive oxygen species (ROS) upon green light irradiation. Here, we show the therapeutic potential of a novel tumor-specific replicating photodynamic viral agent (TelomeKiller) constructed using the human telomerase reverse transcriptase (hTERT) promoter. We investigated the light-induced antitumor effect of TelomeKiller in several types of human cancer cell lines. Relative cell viability was investigated using an XTT assay. The in vivo antitumor effect was assessed using subcutaneous xenografted tumor and lymph node metastasis models. KillerRed accumulation resulted in ROS generation and apoptosis in light-irradiated cancer cells. Intratumoral injection of TelomeKiller efficiently delivered the KillerRed protein throughout the tumors and exhibited a long-lasting antitumor effect with repeated administration and light irradiation in mice. Moreover, intratumorally injected TelomeKiller could spread into the regional lymph node area and eliminate micrometastasis with limited-field laser irradiation. Our results suggest that KillerRed has great potential as a novel photosensitizer if delivered with a tumor-specific virus-mediated delivery system. TelomeKiller-based PDT is a promising antitumor strategy to efficiently eradicate tumor cells. PMID:26625896

  5. Predicting photodynamic therapy efficacy with photoacoustic imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Mallidi, Srivalleesha; Mai, Zhiming; Khan, Amjad P.; Hasan, Tayyaba

    2016-03-01

    Photodynamic therapy (PDT) is a photochemistry based cytotoxic technique that imparts cellular damage via excitation of a photosensitizer with drug-specific wavelength of light. The dose at the treatment site for type II PDT is determined by three factors: photosensitizer (PS) concentration, oxygenation status and delivered light irradiance. Most of the FDA approved photosensitizers in their triplet-excited state generate cytotoxic species by reacting with the ground state oxygen that is available in the surrounding environment. Given the inter- and intra-subject variability in the uptake of the photosensitizer and the distribution of oxygen in the tumor, understanding the interplay between these dose parameters could aid in determining photodynamic therapy efficacy. Previously several studies have discussed the interplay between the dose parameters using shown point measurements and 2D imaging systems. Using various subcutaneous and orthotopic mouse models we will demonstrate the utility of a non-invasive non-ionizing photoacoustic imaging modality to determine efficacy and predict treatment response in Benzoporphyrin derivative (BPD) or Aminolevulinic acid (ALA) based PDT. We further compare the predictive capability of photoacoustic imaging with the more predominantly used fluorescence imaging and immunohistochemistry techniques.

  6. Active and passive control of zinc phthalocyanine photodynamics.

    PubMed

    Sharma, Divya; Huijser, Annemarie; Savolainen, Janne; Steen, Gerwin; Herek, Jennifer L

    2013-01-01

    In this work we report on the ultrafast photodynamics of the photosensitizer zinc phthalocyanine (ZnPc) and manipulation thereof. Two approaches are followed: active control via pulse shaping and passive control via strategic manipulation in the periphery of the molecular structure. The objective of both of these control experiments is the same: to enhance the yield of the functional pathway and to minimize loss channels. The aim of the active control experiments is to increase the intersystem crossing yield in ZnPc, which is important for application in photodynamic therapy (PDT). Pulse shaping allowed an improvement in triplet to singlet ratio of 15% as compared to a transform-limited pulse. This effect is ascribed to a control mechanism that utilizes multiphoton pathways to higher-lying states from where intersystem crossing is more likely to occur. The passive control experiments are performed on ZnPc derivatives deposited onto TiO2, serving as a model system of a dye-sensitized solar cell (DSSC). Modification of the anchoring ligand of the molecular structure resulted in an increased rate for electron injection into TiO2 and slower back electron transfer, improving the DSSC efficiency. PMID:24020214

  7. Pulmonary decontamination for photodynamic inactivation with extracorporeal illumination

    NASA Astrophysics Data System (ADS)

    Geralde, Mariana C.; Leite, Ilaiáli S.; Inada, Natalia M.; Grecco, Clóvis; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Infectious pneumonia is a major cause of morbidity and mortality, despite advances in diagnostics and therapeutics in pulmonary infections. One of the major difficulties associated with the infection comes from the high rate of antibiotic resistant microorganisms, claiming for the use of alternative techniques with high efficiency and low cost. The photodynamic inactivation (PDI) is emerging as one of the great possibilities in this area, once its action is oxidative, not allowing microorganism develops resistance against the treatment. PDI for decontamination pulmonary has potential for treatment or creating better conditions for the action of antibiotics. In this study, we are developing a device to implement PDI for the treatment of lung diseases with extracorporeal illumination. To validate our theory, we performed measurements in liquid phantom to simulate light penetration in biological tissues at various fluency rates, the temperature was monitored in a body of hairless mice and the measurements of light transmittance in this same animal model. A diode laser emitting at 810 nm in continuous mode was used. Our results show 70% of leakage at 0.5 mm of thickness in phantom model. The mouse body temperature variation was 5.4 °C and was observed light transmittance through its chest. These results are suggesting the possible application of the extracorporeal illumination using infrared light source. Based on these findings, further studies about photodynamic inactivation will be performed in animal model using indocyanine green and bacteriochlorin as photosensitizers. The pulmonary infection will be induced with Streptococcus pneumoniae and Klebsiella pneumoniae.

  8. Photodynamic evaluation of tetracarboxy-phthalocyanines in model systems.

    PubMed

    Alonso, Lais; Sampaio, Renato N; Souza, Thalita F M; Silva, Rodrigo C; Neto, Newton M Barbosa; Ribeiro, Anderson O; Alonso, Antonio; Gonçalves, Pablo J

    2016-08-01

    The present work reports the synthesis, photophysical and photochemical characterization and photodynamic evaluation of zinc, aluminum and metal free-base tetracarboxy-phthalocyanines (ZnPc, AlPc and FbPc, respectively). To evaluate the possible application of phthalocyanines as a potential photosensitizer the photophysical and photochemical characterization were performed using aqueous (phosphate-buffered solution, PBS) and organic (dimethyl sulfoxide, DMSO) solvents. The relative lipophilicity of the compounds was estimated by the octanol-water partition coefficient and the photodynamic activity evaluated through the photooxidation of a protein and photohemolysis. The photooxidation rate constants (k) were obtained and the hemolytic potential was evaluated by the maximum percentage of hemolysis achieved (Hmax) and the time (t50) to reach 50% of the Hmax. Although these phthalocyanines are all hydrophilic and possess very low affinity for membranes (log PO/W=-2.0), they led to significant photooxidation of bovine serum albumin (BSA) and photohemolysis. Our results show that ZnPc was the most efficient photosensitizer, followed by AlPc and FbPc; this order is the same as the order of the triplet and singlet oxygen quantum yields (ZnPc>AlPc>FbPc). Furthermore, together, the triplet, fluorescence and singlet oxygen quantum yields of zinc tetracarboxy-phthalocyanines suggest their potential for use in theranostic applications, which simultaneously combines photodiagnosis and phototherapy. PMID:27232148

  9. 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.

  10. 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.

  11. Optical Imaging, Photodynamic Therapy and Optically-Triggered Combination Treatments

    PubMed Central

    Hasan, Tayyaba

    2015-01-01

    Optical imaging is becoming increasingly promising for real-time image-guided resections and combined with photodynamic therapy (PDT), a photochemistry-based treatment modality, optical approaches can be intrinsically “theranostic”. Challenges in PDT include precise light delivery, dosimetry and photosensitizer tumor localization to establish tumor selectivity, and like all other modalities, incomplete treatment and subsequent activation of molecular escape pathways are often attributable to tumor heterogeneity. Key advances in molecular imaging, target-activatable photosensitizers and optically active nanoparticles that provide both cytotoxicity and a drug release mechanism, have opened exciting avenues to meet these challenges. The focus of the review is optical imaging in the context of PDT but the general principles presented are applicable to many of the conventional approaches to cancer management. We highlight the role of optical imaging in providing structural, functional and molecular information regarding photodynamic mechanisms of action, thereby advancing PDT and PDT-based combination therapies of cancer. These advances represent a PDT renaissance with increasing applications of clinical PDT as a frontline cancer therapy working in concert with fluorescence-guided surgery, chemotherapy and radiation. PMID:26049699

  12. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-03-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

  13. In vitro study for photodynamic therapy using Fotolon in glioma treatment

    NASA Astrophysics Data System (ADS)

    Abdel Hamid, Sara; Zimmermann, Wolfgang; Huettenberger, Dirk; Wittig, Rainer; Abdel Kader, Mahmoud; Stepp, Herbert

    2015-07-01

    Several forms of Chlorin e6 and its derivatives are reported as efficient photosensitizers (PS) studied in Photodynamic Therapy (PDT) for oncologic applications. Fotolon® is a pure form of Chlorin e6 trisodium salt developed by Apocare Pharma.

  14. An ethylene-glycol decorated ruthenium(ii) complex for two-photon photodynamic therapy.

    PubMed

    Boca, Sanda C; Four, Mickaël; Bonne, Adeline; van der Sanden, Boudewijn; Astilean, Simion; Baldeck, Patrice L; Lemercier, Gilles

    2009-08-14

    A novel water-soluble Ru(ii) complex has been prepared, which represents a promising new class of selective two-photon sensitizers for use in photodynamic therapy within a confined space. PMID:19617993

  15. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part five of a five-part series

    PubMed Central

    2009-01-01

    The use of photodynamic therapy has increased dramatically over the past several years. More clinicians are utilizing this therapy and additional indications for its use have become available. The photosensitizers that are utilized for this therapy differ and have been used differently over the past 10 years of our experience with photodynamic therapy. This manuscript examines the photosensitizers and the differences between them as well as reviews the literature on photosensitizers. PMID:20967181

  16. Device for fluorescent control and photodynamic therapy of age-related macula degeneration

    NASA Astrophysics Data System (ADS)

    Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

    2004-07-01

    Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

  17. Development of Singlet Oxygen Luminescence Kinetics during the Photodynamic Inactivation of Green Algae.

    PubMed

    Bornhütter, Tobias; Pohl, Judith; Fischer, Christian; Saltsman, Irena; Mahammed, Atif; Gross, Zeev; Röder, Beate

    2016-01-01

    Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in order to determine optimization parameters. The observation of singlet oxygen luminescence kinetics proved to be a very effective approach towards understanding mechanisms on a cellular level. In this study, the first two-dimensional measurement of singlet oxygen kinetics in phototrophic microorganisms on surfaces during photodynamic inactivation is presented. We established a system of reproducible algae samples on surfaces, incubated with two different cationic, antimicrobial potent photosensitizers. Fluorescence microscopy images indicate that one photosensitizer localizes inside the green algae while the other accumulates along the outer algae cell wall. A newly developed setup allows for the measurement of singlet oxygen luminescence on the green algae sample surfaces over several days. The kinetics of the singlet oxygen luminescence of both photosensitizers show different developments and a distinct change over time, corresponding with the differences in their localization as well as their photosensitization potential. While the complexity of the signal reveals a challenge for the future, this study incontrovertibly marks a crucial, inevitable step in the investigation of photodynamic inactivation of biofilms: it shows the feasibility of using the singlet oxygen luminescence kinetics to investigate photodynamic effects on surfaces and thus opens a field for numerous investigations. PMID:27089311

  18. Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT

    NASA Astrophysics Data System (ADS)

    Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.

    2012-10-01

    Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.

  19. Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

    PubMed Central

    2010-01-01

    Background Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. The most dangerous are methicillin-resistant S. aureus (MRSA) strains, resistant not only to all β-lactam antibiotics but also to other antimicrobials. An alarming increase in antibiotic resistance spreading among pathogenic bacteria inclines to search for alternative therapeutic options, for which resistance can not be developed easily. Among others, photodynamic inactivation (PDI) of S. aureus is a promising option. Photodynamic inactivation is based on a concept that a non toxic chemical, called a photosensitizer upon excitation with light of an appropriate wavelength is activated. As a consequence singlet oxygen and other reactive oxygen species (e.g. superoxide anion) are produced, which are responsible for the cytotoxic effect towards bacterial cells. As strain-dependence in photodynamic inactivation of S. aureus was observed, determination of the molecular marker(s) underlying the mechanism of the bacterial response to PDI treatment would be of great clinical importance. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance. Results The effectiveness of photodynamic inactivation towards S. aureus and its Sod isogenic mutants deprived of either of the two superoxide dismutase activities, namely SodA or SodM or both of them showed similar results, regardless of the Sod status in TSB medium. On the contrary, in the CL medium (without Mn++ ions) the double SodAM mutant was highly susceptible to photodynamic inactivation. Among 8 clinical isolates of S. aureus analyzed (4 MRSA and 4 MSSA), strains highly resistant and strains highly vulnerable to photodynamic inactivation were noticed. We observed that Sod activity as well as sodA and sodM transcript level increases after protoporphyrin IX-based photodynamic treatment but only in PDI-sensitive strains. Conclusions We

  20. One-time ray-tracing optimization method and its application to the design of an illuminator for a tube photo-bioreactor.

    PubMed

    Chu, Shu-Chun; Yang, Hai-Li; Liao, Yi-Hong; Wu, Hong-Yu; Wang, Chi

    2014-03-10

    This study details a one-time ray-tracing optimization method for the optimization of LED illumination systems [S.-C. Chu and H.-L. Yang, "One-time ray-tracing method for the optimization of illumination system," in Proceedings of International Conference on Optics in Precision Engineering and Nanotechnology (icOPEN, 2013), 87692M]. This method optimizes the performance of illumination systems by modifying the light source's radiant intensity distribution with a freeform lens, instead of modifying the illumination system structure. Because illumination system structures are unchanged in the design process, a designer can avoid the common problems faced when designing illumination systems, i.e., the repeated and time-consuming ray-tracing process when optimizing the illumination system parameters. The easy approaches of the proposed optimization method to sample the target illumination areas and to divide the light source radiant intensity distribution make the proposed method can be applied to both direct-lit and non-direct-lit illumination systems. To demonstrate the proposed method, this study designs an illuminator for a tube photo-bioreactor using the proposed one-time ray-tracing method. A comparison shows that in the designing of the photo-bioreactor, tracing all rays one time requires about 13 hours, while optimizing the light source's radiant intensity distribution requires only about twenty minutes. The considerable reduction in the ray-tracing time shows that the proposed method is a fast and effective way to design illumination systems. PMID:24663876

  1. 5 CFR 839.1122 - Does receipt of a one-time payment of retirement contributions as a death benefit prevent me from...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Does receipt of a one-time payment of retirement contributions as a death benefit prevent me from electing CSRS Offset? 839.1122 Section 839.1122... contributions as a death benefit prevent me from electing CSRS Offset? You may still elect CSRS Offset...

  2. Comparative study of two kinds of repeated photodynamic therapy strategies in breast cancer by using a sensitizer, sinoporphyrin sodium.

    PubMed

    Xiong, Wenli; Wang, Xiaobing; Hu, Jianmin; Liu, Yichen; Liu, Quanhong; Wang, Pan

    2016-07-01

    Sinoporphyrin sodium (DVDMS) is a newly identified photosensitizer that was isolated from Photofrin. Experimental and clinical results have demonstrated that repeated application of PDT greatly improved the therapeutic efficacy. Here, we comparatively studied two kinds of photodynamic therapy (PDT) strategies by using DVDMS (2mg/kg) in murine breast cancer 4T1 xenograft model to provide evidence which strategy exerts a better antitumor effect. Regimen (1): DVDMS was injected one time into tumor-bearing mice, which were then repeatedly exposed to 50J/cm(2) light 24h, 30h and 36h later. Regimen (2): DVDMS was injected 3 times and mice exposed to 50J/cm(2) light 24h after each injection, with 5days intervals between each DVDMS injection. On day 21 after the tumor cell injection, in regimen (1) the tumor volume inhibition ratio was reached to 85.75±7.60%. While at the same day the inhibition ratio was 65.74±8.64% of regimen (2). Additionally, regimen (1) appeared to more effectively initiate tumor tissue destruction and cancer cell apoptosis, inhibit lung metastasis, suppress cancer cell proliferation and angiogenesis. Moreover, no obvious effect on body weight and other side effects were observed in the treated mice. These results suggest that regimen (1) might be a potentially efficient strategy against breast cancer. PMID:27162175

  3. Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy.

    PubMed

    Qin, Chenchen; Fei, Jinbo; Wang, Anhe; Yang, Yang; Li, Junbai

    2015-12-21

    To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm(-2), 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic. PMID:26574662

  4. 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

  5. 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%.

  6. In vivo monitoring of photosensitizer fluorescence during photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Stringer, Mark R.; Robinson, Dominic J.; Hudson, Emma J.; Smith, Michael A.

    1995-03-01

    A method is presented of monitoring the low level fluorescence emitted by the photosensitizing agent protoporphyrin IX during superficial photodynamic therapy of skin carcinomas, using 630 nm illumination. A fiber optic probe samples the light field which is filtered and recorded by an optical spectrum analyzer. The technique is minimally invasive and can proceed concurrently with light dosimetry measurements. This paper presents in vitro data that define the sensitivity and selectivity of the technique, along with preliminary in vivo measurements. These indicate that it is the rate of phototransformation of the photosensitizer, rather than the total light dose, that determines the optimum treatment duration. Clinically effective treatment therefore depends upon achieving a threshold concentration of drug throughout the volume of the lesion. In this way the effect of phototransformation does not inactivate the drug before complete tumor necrosis occurs.

  7. 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.

  8. 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.

  9. 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.

  10. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection

    PubMed Central

    Fu, Xiu-jun; Fang, Yong; Yao, Min

    2013-01-01

    Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

  11. Scintillating Nanoparticles as Energy Mediators for Enhanced Photodynamic Therapy.

    PubMed

    Kamkaew, Anyanee; Chen, Feng; Zhan, Yonghua; Majewski, Rebecca L; Cai, Weibo

    2016-04-26

    Achieving effective treatment of deep-seated tumors is a major challenge for traditional photodynamic therapy (PDT) due to difficulties in delivering light into the subsurface. Thanks to their great tissue penetration, X-rays hold the potential to become an ideal excitation source for activating photosensitizers (PS) that accumulate in deep tumor tissue. Recently, a wide variety of nanoparticles have been developed for this purpose. The nanoparticles are designed as carriers for loading various kinds of PSs and can facilitate the activation process by transferring energy harvested from X-ray irradiation to the loaded PS. In this review, we focus on recent developments of nanoscintillators with high energy transfer efficiency, their rational designs, as well as potential applications in next-generation PDT. Treatment of deep-seated tumors by using radioisotopes as an internal light source will also be discussed. PMID:27043181

  12. [Use of nanoparticles (NP) in photodynamic therapy (PDT) against cancer].

    PubMed

    Roblero-Bartolón, Gabriela Victoria; Ramón-Gallegos, Eva

    2015-01-01

    Nanotechnology is a promising interdisciplinary field for developing improved methods of diagnosis and treatment of different diseases, including cancer. Give their optical, magnetic, and structural property, the nanoparticles have been proposed to be use in the development of unconventional treatments for cancer such as photodynamic therapy (PDT). In PDT, a photosensitizing agent is used that accumulates in tumor cells, generating reactive oxygen species that causes the death of malignant cells after irradiation with light at a particular wavelength. However, the use of PDT presents different problems in its application due to the characteristics of hydrophobicity of the photosensitizers, which hinder the efficiency of administration and treatment. It is here where the use of nanoparticles is proposed as a delivery vehicle to optimize treatment application. In this review we describe the use of nanoparticles coupled to PDT in the treatment of cancer and its molecular mechanism of action. PMID:25739488

  13. 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.

  14. 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.

  15. Self-assembled liposomal nanoparticles in photodynamic therapy

    PubMed Central

    Sadasivam, Magesh; Avci, Pinar; Gupta, Gaurav K.; Lakshmanan, Shanmugamurthy; Chandran, Rakkiyappan; Huang, Ying-Ying; Kumar, Raj; Hamblin, Michael R.

    2013-01-01

    Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers (PS) together with harmless visible light of the appropriate wavelength to produce reactive oxygen species that kill unwanted cells. Because many PS are hydrophobic molecules prone to aggregation, numerous drug delivery vehicles have been tested to solubilize these molecules, render them biocompatible and enhance the ease of administration after intravenous injection. The recent rise in nanotechnology has markedly expanded the range of these nanoparticulate delivery vehicles beyond the well-established liposomes and micelles. Self-assembled nanoparticles are formed by judicious choice of monomer building blocks that spontaneously form a well-oriented 3-dimensional structure that incorporates the PS when subjected to the appropriate conditions. This self-assembly process is governed by a subtle interplay of forces on the molecular level. This review will cover the state of the art in the preparation and use of self-assembled liposomal nanoparticles within the context of PDT. PMID:24348377

  16. Liposome-administered tetramethylhematoporphyrin (TMHP) as a photodynamic agent

    NASA Astrophysics Data System (ADS)

    Reich, Ella D.; Bachor, Ruediger; Miller, Kurt; Koenig, Karsten; Repassy, Denes; Hautmann, Richard E.

    1994-03-01

    The purpose of these studies was to determine whether liposomes can deliver the photo- sensitizer TMHP to human bladder carcinoma cells and fibroblast cells, and how effective the photodynamic activity of this photosensitizer is. TMHP was incorporated into small unilamellar liposomes of DPPC. Cellular uptake of TMHP was estimated after extraction with 0.1 N NaOH and by using a fluorescence microscope. Quantitative levels of TMHP in the three cell lines have been expressed in terms of (mu) g per 1.106 cells. PDT was performed for one hour after sensitization using an argon-pumped dye laser at 630 nm. Compared to the fibroblasts, neither a selective uptake of TMHP nor an increased effect of phototoxicity did occur in the tumor cell lines. PDT efficiency is dependent on cell line, dose and fluence rate.

  17. 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.

  18. Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kempa, Marta; Kozub, Patrycja; Kimball, Joseph; Rojkiewicz, Marcin; Kuś, Piotr; Gryczyński, 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.

  19. Photodynamic therapy in dermatology: state-of-the-art.

    PubMed

    Babilas, Philipp; Schreml, Stephan; Landthaler, Michael; Szeimies, Rolf-Markus

    2010-06-01

    Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications. PMID:20584250

  20. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  1. 5-ALA-assisted photodynamic therapy in canine prostates

    NASA Astrophysics Data System (ADS)

    Sroka, Ronald; Muschter, Rolf; Knuechel, Ruth; Steinbach, Pia; Perlmutter, Aaron P.; Martin, Thomas; Baumgartner, Reinhold

    1996-05-01

    Photodynamic therapy (PDT) and interstitial thermotherapy are well known treatment modalities in urology. The approach of this study is to combine both to achieve a selective treatment procedure for benign prostatic hyperplasia (BPH) and prostate carcinoma. Measurements of thy in-vivo pharmacokinetics of 5-ALA induced porphyrins by means of fiber assisted ratiofluorometry showed a maximum fluorescence intensity at time intervals of 3 - 4 h post administration. Fluorescence microscopy at that time showed bright fluorescence in epithelial cells while in the stroma fluorescence could not be observed. Interstitial PDT using a 635-nm dye laser with an irradiation of 50 J/cm2 resulted in a nonthermic hemorrhagic lesion. The lesion size did not change significantly when an irradiation of 100 J/cm2 was used. The usefulness of PDT for treating BPH as well as prostate carcinoma has to be proven in further studies.

  2. Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles.

    PubMed

    Bucharskaya, Alla; Maslyakova, Galina; Terentyuk, Georgy; Yakunin, Alexander; Avetisyan, Yuri; Bibikova, Olga; Tuchina, Elena; Khlebtsov, Boris; Khlebtsov, Nikolai; Tuchin, Valery

    2016-01-01

    Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells. PMID:27517913

  3. Fat tissue staining and photodynamic/photothermal effects

    NASA Astrophysics Data System (ADS)

    Tuchin, Valery V.; Altshuler, Gregory B.; Yanina, Irina Yu.; Kochubey, Vyacheslav I.; Simonenko, Georgy V.

    2010-02-01

    Cellulite is considered as a disease of the subcutaneous fat layer that appears mostly in women and consists of changes in fat cell accumulation together with disturbed lymphatic drainage, affecting the external appearance of the skin. The photodynamic and selective photothermal treatments may provide reduction the volume of regional or sitespecific accumulations of subcutaneous adipose tissue on the cellular level. We hypothesize that light irradiation of stained fat tissue at selected temperature leads to fat cell lypolytic activity (the enhancement of lipolysis of cell triglycerides due to expression of lipase activity and cell release of free fat acids (FFAs) due to temporal cell membrane porosity), and cell killing due to apoptosis caused by the induced fat cell stress and/or limited cell necrosis.

  4. 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.

  5. Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy

    PubMed Central

    Ragàs, Xavier; Sánchez-García, David; Ruiz-González, Rubén; Dai, Tianhong; Agut, Montserrat; Hamblin, Michael R.; Nonell, Santi

    2010-01-01

    Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines and phenothiazinium salts, with cationic charges at physiological pH values. However derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse 3rd degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log10 reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm-2 of red light. PMID:20936792

  6. Photodynamic therapy in the prophylactic management of bladder cancer

    NASA Astrophysics Data System (ADS)

    Nseyo, Unyime O.; Lundahl, Scott L.; Merrill, Daniel C.

    1991-06-01

    Nine patients were treated with red light whole bladder photodynamic therapy (WBPDT): five had mucosal involvement (Ta) and four submucosal invasion (T1). Patients received slow intravenous injection with 2mg/kg body weight of photofrin 48-72 hours before undergoing global light treatment via a 22-French cystoscope with a 400-micron quartz fiber bulb (isotropic) tip fiber. Three months after PDT, eight of the patients had normal cystoscopy, and negative biopsy and urine cytology. Two patients who had recurrences at six and twelve months were retreated with a higher dose (20 J/cm2). They had no increased morbidity and no evidence of recurrent disease six months later. WBPDT should be considered as an important alternative treatment for patients who have recurrent or refractory superficial bladder cancer.

  7. Systemic estimation of the effect of photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

    1997-12-01

    The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

  8. Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles

    PubMed Central

    Bucharskaya, Alla; Maslyakova, Galina; Terentyuk, Georgy; Yakunin, Alexander; Avetisyan, Yuri; Bibikova, Olga; Tuchina, Elena; Khlebtsov, Boris; Khlebtsov, Nikolai; Tuchin, Valery

    2016-01-01

    Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells. PMID:27517913

  9. Evaluation of quantum dots for photodynamic therapy (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Dayal, Smita; Krolicki, Robert; Burda, Clemens

    2005-04-01

    Photodynamic therapy (PDT) is an emerging therapy for cancer treatment that shows the greater selectivity towards the malignant cells. Semiconductor nanoparticles are a novel class of photosensitizers with properties that are not easily available with conventional PDT reagents. Their potential properties such as improved luminescence, resistance to photobleaching, and the possibility to modify the surface chemically make them suitable candidates for PDT. In this report, we discuss the synthesis of ternary CdSe1-x Tex nanoparticles along with well known CdSe QDs and their potential in generating the singlet oxygen state by Foerster Resonance Energy Transfer (FRET) to a PDT reagent or by direct triplet-triplet energy transfer to molecular oxygen.

  10. A review of photodynamic therapy in cutaneous leishmaniasis.

    PubMed

    van der Snoek, E M; Robinson, D J; van Hellemond, J J; Neumann, H A M

    2008-08-01

    We present a review of six clinical studies investigating the use of photodynamic therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT using a range of treatment schedules following topical application of aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and hyperpigmentation. Few mechanistic studies have addressed the principles underlying the use of PDT for CL. All six reviewed papers suggest that PDT with porphyrin precursors is relatively effective in treating CL. Data are still limited, and PDT cannot at this point be recommended in routine clinical practice. The mechanism of action of this promising therapeutic modality needs to investigated further and additional controlled trials need to be performed. PMID:18624853

  11. 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

  12. 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

  13. Photodynamic Therapy for Gynecological Diseases and Breast Cancer

    PubMed Central

    Shishkova, Natashis; Kuznetsova, Olga; Berezov, Temirbolat

    2012-01-01

    Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy. PMID:23691448

  14. Endoscopic photodynamic therapy of tumors using gold vapor laser

    NASA Astrophysics Data System (ADS)

    Kuvshinov, Yury P.; Poddubny, Boris K.; Mironov, Andrei F.; Ponomarev, Igor V.; Shental, V. V.; Vaganov, Yu. E.; Kondratjeva, T. T.; Trofimova, E. V.

    1996-01-01

    Compact sealed-off gold vapor laser (GVL) with 2 W average power and 628 nm wavelength was used for endoscopic photodynamic therapy in 20 patients with different tumors in respiratory system and upper gastrointestinal tract. Russian-made hematoporphyrin derivative (Hpd) `Photohem' was used as a photosensitizer. It was given intravenously at a dose of 2 - 2.5 mg/kg body weight 48 hours prior to tumor illumination with 628 nm light from GVL. Intermittent irradiation with GVL was done through flexible endoscope always under local anaesthesia at a power of 200 - 400 mW/sm2 and a dose of 150 - 400 J/sm2. 80% patients showed complete or partial response depending on stage of tumor. In cases of early gastric cancer all patients had complete remission with repeated negative biopsies. No major complication occurred.

  15. 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.

  16. 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.

  17. Effects of photodynamic therapy on human glioma spheroids

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Sun, Chung-Ho; Chu, Eugene A.; Hirschberg, Henry; Tromberg, Bruce J.

    1999-07-01

    The poor prognosis for patients with malignant brain neoplasm has led to a search for better treatment modalities. Although gliomas are considered to be disseminated tumors in the brain, most recur at the site of the previous tumor resection. Improved local control would thus be of clear benefit. The utility of photodynamic therapy (PDT) in the treatment of brain neoplasms is investigated using a human glioma spheroid model. Specifically, the effects of PDT on human glioma spheroids are investigated using PhotofrinTM and 56-aminolevulinic acid (ALA). The effects of various irradiation schemes were monitored using a simple growth assay. A growth delay was observed at an optical fluence of approximately 35 J cm-2 for spheroids incubated in Photofrin. Spheroids incubated in ALA were unaffected by the PDT treatment regimens examined in this study. This was most likely a result of inadequate photosensitizer concentration.

  18. Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue.

    PubMed

    Kariminezhad, H; Habibi, M; Mirzababayi, N

    2015-07-01

    Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV-Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75 nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mg g(-1)). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency. PMID:25900556

  19. Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.

    PubMed

    Takahashi, Hidetoshi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

    2014-10-01

    Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm2 and 1 μg/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. PMID:25226792

  20. 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

  1. Photodynamic damage of glial cells in crayfish ventral nerve cord

    NASA Astrophysics Data System (ADS)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2011-03-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  2. Photodynamic damage of glial cells in crayfish ventral nerve cord

    NASA Astrophysics Data System (ADS)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2010-10-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  3. Photodynamic effect of curcumin on NPC/CNE2 cells.

    PubMed

    Koon, H; Leung, Albert W N; Yue, Kevin K M; Mak, Naiki K

    2006-01-01

    Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China. Radiotherapy is the primary treatment of NPC, but the rate of tumor recurrence is significant. Photodynamic therapy (PDT) and the use of natural compounds become one of the new approaches in the investigation of NPC treatment. PDT is an alternate method of cancer treatment while curcumin (CUR) is a compound derived from the traditional Chinese medicinal (TCM) herbs. The purpose of the study focuses on the photodynamic effect of CUR on one of the NPC cell lines, NPC/CNE2. Cytotoxicity and photocytotoxicity of CUR were evaluated by 3-(4,5-dimthyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Uptake kinetics of CUR in NPC/CNE2 was examined by flow cytometry. The mode of cell death induced by CUR was studied by fluorescence microscopy. Summarizing the results, CUR showed dark cytotoxicity as well as photocytotoxic effects on NPC/CNE2 cells. LC50 of CUR in the dark was about 16 microM. The cytotoxicity of CUR was enhanced by the irradiation of visible light and blue filtered light (maximum transmittance at 300 approximately 400 nm) with light doses of 300 kJ/m2 and 60 kJ/m2 respectively. NPC/CNE2 was found to rapidly take up CUR in the first hour of incubation, and the uptake kinetics steadily increased to a plateau level after 20 hr of incubation. Cell shrinkage and membrane bledding appeared under the observation of fluorescence microscopy. Such evidences proved that CUR might induce apoptosis on NPC/CNE2 cells. The preliminary study confirmed that CUR demonstrated dark cytotoxicity and photocytotoxicty to NPC/CNE2. The mode of action is likely to be induced by apoptotic pathway. CUR may be developed as a potential photosensitizer as well as a chemotherapeutic agent in clinical application. PMID:16566718

  4. 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.

  5. Photodynamic therapy repeated without reinjection of Photofrin (porfimer sodium)

    NASA Astrophysics Data System (ADS)

    McCaughan, James S.

    1998-05-01

    Background and objective: To compare the effectiveness in decreasing the amount of obstruction caused by endobronchial tumors when they are retreated with photodynamic therapy (PDT) several weeks after injection of PhotofrinR (porfimer sodium). Study design, materials and methods: The percentage of endobronchial obstruction from tumors before PDT and at the end of toilet bronchoscopy of 91 sites with PDT performed within 4 days after injection of porfimer sodium was compared to that obtained when PDT was repeated without re-injection of porfimer sodium in the time frames 2 - 4 weeks after injection to 11 sites and the period 4 - 8 weeks after injection to 17 sites. All patients were injected intravenously with 60 mg of PhotofrinR per square meter of body surface and all treatments were done with a power density of 500 mW/CF and a light dose of 400 J/CF delivered from cylinder diffusing fibers. Results: Paired Student's t tests and Wilcoxon signed ranks tests showed significant decreases in the percentage of endobronchial obstruction regardless of whether the PDT was first performed or repeated. Unpaired Student's t tests and Mann-Whitney U statistical comparisons showed a significant difference between the decrease of obstruction when treatment was performed within the first 4 days after injection (mean 41%) as compared to the repeated group 2 to 4 weeks after injection (mean 16%) and the group treated 4 to 8 weeks after injection (mean 19%). However there was no significant difference in the amount of decrease of obstruction between the 2 - 4 week group and the 4 - 8 week group. Conclusions: Photodynamic therapy to relieve endobronchial obstruction can be repeated without reinjection of PhotofrinR up to 8 weeks after injection with a significant decrease in the amount of obstruction. However, it will only be about 1/3 as effective as the initial treatment performed within the first four days of injection.

  6. Light-triggered liposomal release: membrane permeabilization by photodynamic action.

    PubMed

    Pashkovskaya, Alina; Kotova, Elena; Zorlu, Yunus; Dumoulin, Fabienne; Ahsen, Vefa; Agapov, Igor; Antonenko, Yuri

    2010-04-20

    Photosensitized damage to liposome membranes was studied by using different dye-leakage assays based on fluorescence dequenching of a series of dyes upon their release from liposomes. Irradiation of liposomes with red light in the presence of a photosensitizer, trisulfonated aluminum phthalocyanine (AlPcS(3)), resulted in the pronounced leakage of carboxyfluorescein, but rather weak leakage of sulforhodamine B and almost negligible leakage of calcein from the corresponding dye-loaded liposomes. The same series of selectivity of liposome leakage was obtained with chlorin e6 that appeared to be more potent than AlPcS(3) in bringing about the photosensitized liposome leakage. Electrically neutral zinc phthalocyanine tetrasubstituted with a glycerol moiety (ZnPcGlyc(4)) was less effective than negatively charged AlPcS(3) in provoking the light-induced liposome permeabilization. On the contrary, both ZnPcGlyc(4) and AlPcS(3) were much more effective than chlorin e6 in sensitizing gramicidin channel inactivation in planar bilayer lipid membranes, thus showing that relative photodynamic efficacy of sensitizers can differ substantially for damaging different membrane targets. The photosensitized liposome permeabilization was apparently associated with oxidation of lipid double bonds by singlet oxygen as evidenced by the mandatory presence of unsaturated lipids in the membrane composition for the photosensitized liposome leakage to occur and the sensitivity of the latter to sodium azide. The fluorescence correlation spectroscopy measurements revealed marked permeability of photodynamically induced pores in liposome membranes for such photosensitizer as AlPcS(3). PMID:20000430

  7. The irradiation parameters investigation of photodynamic therapy on yeast cells

    NASA Astrophysics Data System (ADS)

    Prates, Renato A.; da Silva, Eriques G.; Yamada, Aécio M., Jr.; Suzuki, Luis C.; Paula, Claudete R.; Ribeiro, Martha S.

    2008-03-01

    It has been proposed that photodynamic therapy (PDT) can inactivate microbial cells. A range of photosensitizers and light sources were reported as well as different fluence parameters and dye concentrations. However, much more knowledge regarding to the role of fluences, irradiation time and irradiance are required for a better understanding of the photodynamic efficiency. The aims of this study were to investigate the role of light parameters on the photoinactivation of yeast cells, and compare cell survivors in different growing phases following PDT. To perform this study, a suspension (10 6cfu/mL) of Candida albicans ATCC-90028 was used in log and stationary-phase. Three irradiances 100mW/cm2, 200mW/cm2 and 300mW/cm2 were compared under 3min, 6min and 9min of irradiation, resulting in fluences of 18, 36, 54, 72,108 and 162J/cm2. The light source used was a laser emitting at 660nm with output power of 30, 60 and 90mW. As photosensitizer, 100μΜ methylene blue was used. PDT was efficient against yeast cells (6 log reduction) in log and stationary-phase. Neither photosensitizer nor light alone presented any reduction of cell viability. The increase of irradiance and time of irradiation showed a clearly improvement of cell photoinactivation. Interestingly, the same fluences in different irradiances presented dissimilar effects on cell viability. The irradiance and time of irradiation are important in PDT efficiency. Fluence per se is not the best parameter to compare photoinativation effects on yeast cells. The growing-phases presented the same susceptibility under C. albicans photoinactivation.

  8. Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.

    PubMed

    Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang; Chen, Jui-Lin; Zhang, Hongyong; Lac, Diana; Zhang, Hua; Ferrara, Katherine W; Wachsmann-Hogiu, Sebastian; Li, Tianhong; Airhart, Susan; deVere White, Ralph; Lam, Kit S; Pan, Chong-Xian

    2016-10-01

    The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic. PMID:27479049

  9. Quinones as photosensitizer for photodynamic therapy: ROS generation, mechanism and detection methods.

    PubMed

    Rajendran, M

    2016-03-01

    Photodynamic therapy (PDT) is based on the dye-sensitized photooxidation of biological matter in the target tissue, and utilizes light activated drugs for the treatment of a wide variety of malignancies. Quinones and porphyrins moiety are available naturally and involved in the biological process. Quinone metabolites perform a variety of key functions in plants which includes pathogen protection, oxidative phosphorylation, and redox signaling. Quinones and porphyrin are biologically accessible and will not create any allergic effects. In the field of photodynamic therapy, porphyrin derivatives are widely used, because it absorb in the photodynamic therapy window region (600-900 nm). Hence, researchers synthesize drugs based on porphyrin structure. Benzoquinone and its simple polycyclic derivatives such as naphthaquinone and anthraquinones absorb at lower wavelength region (300-400 nm), which is lower than porphyrin. Hence they are not involved in PDT studies. However, higher polycyclic quinones absorb in the photodynamic therapy window region (600-900 nm), because of its conjugation and can be used as PDT agents. Redox cycling has been proposed as a possible mechanism of action for many quinone species. Quinones are involved in the photodynamic as well as enzymatic generation of reactive oxygen species (ROS). Generations of ROS may be measured by optical, phosphorescence and EPR methods. The photodynamically generated ROS are also involved in many biological events. The photo-induced DNA cleavage by quinones correlates with the ROS generating efficiencies of the quinones. In this review basic reactions involving photodynamic generation of ROS by quinones and their biological applications were discussed. PMID:26241780

  10. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    PubMed

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  11. Photodynamic effect of novel chlorin e6 derivatives on a single nerve cell.

    PubMed

    Uzdensky, A B; Dergacheva, O Y; Zhavoronkova, A A; Reshetnikov, A V; Ponomarev, G V

    2004-03-12

    Chlorin e(6) and its derivatives are promising sensitizers for photodynamic therapy (PDT). In order to compare the photodynamic effects of 8 novel derivatives of chlorin e(6) and to explore some mechanisms of their effects at the cellular level, we studied PDT-induced changes in bioelectric activity of crayfish mechanoreceptor neuron that was used as a sensitive experimental model. Neurons were insensitive to red laser irradiation (632.8 nm; 0.3 W/cm(2)) or to photosensitizers alone, but changed firing rate and died under the photodynamic effect of nanomolar concentrations of sensitizers. The dynamics of neuron responses depended on photosensitizer type and concentration. The dependence of neuron lifetime on photosensitizer concentration allowed comparing efficiencies of different photosensitizers. Radachlorin was the most potent photosensitizer comparable with mTHPC. High photodynamic efficiency of some chlorin e(6) derivatives was related to weak dependence of neuron lifetime on sensitizer concentration, indicating to the initiation of 2-3 secondary processes such as free radical membrane damage by one absorbed photon. Photodynamic efficiency of sensitizers depended on amphiphilicity influencing their intracellular localization. PMID:14969720

  12. Prevention of Distant Lung Metastasis After Photodynamic Therapy Application in a Breast Cancer Tumor Model.

    PubMed

    Longo, João Paulo Figueiró; Muehlmann, Luis Alexandre; Miranda-Vilela, Ana Luisa; Portilho, Flávia Arruda; de Souza, Ludmilla Regina; Silva, Jaqueline Rodrigues; Lacava, Zulmira Guerrero Marques; Bocca, Anamelia Lorenzetti; Chaves, Sacha Braun; Azevedo, Ricardo Bentes

    2016-04-01

    The objective of this study was to investigate the activity of photodynamic therapy mediated by aluminum-chlorophthalocyanine contained in a polymeric nanostructured carrier composed by methyl vinyl ether-co-maleic anhydride (PVM/MA) against local subcutaneous breast cancer tumors and its effects against distant metastasis in a mouse tumor model. In our results, we observed a decrease in breast cancer tumor growth, prevention of distant lung metastases, and a significant increased survival in mice treated with photodynamic therapy. In addition to these results, we observed that tumor-bearing mice without treatment developed a significant extension of liver hematopoiesis that was significantly reduced in mice treated with photodynamic therapy. We hypothesized and showed that this reduction in (1) metastasis and (2) liver hematopoiesis may be related to the systemic activity of immature hematopoietic cells, specifically the myeloid-derived suppressor cells, which were suppressed in mice treated with photodynamic therapy. These cells produce a tolerogenic tumor environment that protects tumor tissues from immunological surveillance. Therefore, we suggest that photodynamic therapy could be employed in combination with other conventional therapies; such as surgery and radiotherapy, to improve the overall survival of patients diagnosed with breast cancer, as observed in our experimental resuIts. PMID:27301195

  13. Oral proliferative verrucous leukoplakia treated with the photodynamic therapy: a case report

    PubMed Central

    Romeo, Umberto; Russo, Nicola; Palaia, Gaspare; Tenore, Gianluca; Del Vecchio, Alessandro

    2014-01-01

    Summary Aims About 60% of the oral cancer arise on a pre-existent potentially malignant disorder of oral mucosa like the oral proliferative verrucous leukoplakia. The treatment with the photodynamic therapy of these lesions represents, in the last years, an innovative, non-invasive and effective therapeutic possibility to achieve the secondary prevention of oral cancer. In the last decade, case reports have described patients with similar treated through a photochemical reaction induced by laser light. The aim of this study is to evaluate the effectiveness of the topical 5-ALA photodynamic therapy in the treatment of a case of Oral proliferative verrucous leukoplakia. Case report A female patient of 80 years old affected by white verrucous plaques on the right buccal mucosa was recruited for our case report. The right side lesion was treated with the photodynamic therapy with topical administered 5-aminolevulinic acid using the 635 nm laser light to activate the photosensitizer. Results The lesion showed complete response after 4 sessions of photodynamic therapy and no recurrence was noticed after 12 months. Conclusions The photodynamic therapy can be considered an effective treatment in the management of oral verrucous proliferative leukoplakia, but more clinical trials, with prolonged follow-up controls, are necessary to evaluate its effectiveness in the mid and long time period. PMID:25002922

  14. 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

  15. Photodynamic inactivation of microorganisms which cause pulmonary diseases with infrared light: an in vitro study

    NASA Astrophysics Data System (ADS)

    Leite, Ilaiáli S.; Geralde, Mariana C.; Salina, Ana C.; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.; Inada, Natalia M.

    2014-03-01

    Lower respiratory infections are among the leading causes of death worldwide. In this study, it was evaluated the interaction of indocyanine green, a photosensitizer activated by infrared light, with alveolar macrophages and the effectiveness of the photodynamic therapy using this compound against Streptococcus pneumoniae . Initial experiments analyzed indocyanine green toxicity to alveolar macrophages in the dark with different drug concentrations and incubation times, and macrophage viability was obtained with the MTT method. The average of the results showed viability values below 90% for the two highest concentrations. Experiments with Streptococcus pneumoniae showed photodynamic inactivation with 10 μM indocyanine green solution. Further experiments with the bacteria in co-culture with AM will be conducted verifying the photodynamic inactivation effectiveness of the tested drug concentrations and incubation periods using infrared light.

  16. Photodynamic antimicrobial effects of bis-indole alkaloid indigo from Indigofera truxillensis Kunth (Leguminosae).

    PubMed

    Andreazza, Nathalia Luiza; de Lourenço, Caroline C; Stefanello, Maria Élida Alves; Atvars, Teresa Dib Zambon; Salvador, Marcos José

    2015-05-01

    Multidrug-resistant microbial infections represent an exponentially growing problem affecting communities worldwide. Photodynamic therapy is a promising treatment based on the combination of light, oxygen, and a photosensitizer that leads to reactive oxygen species production, such as superoxide (type I mechanism) and singlet oxygen (type II mechanism) that cause massive oxidative damage and consequently the host cell death. Indigofera genus has gained considerable interest due its mutagenic, cytotoxic, and genotoxic activity. Therefore, this study was undertaken to investigate the effect of crude extracts, alkaloidal fraction, and isolated substance derived from Indigofera truxillensis in photodynamic antimicrobial chemotherapy on the viability of bacteria and yeast and evaluation of mechanisms involved. Our results showed that all samples resulted in microbial photoactivation in subinhibitory concentration, with indigo alkaloid presenting a predominant photodynamic action through type I mechanism. The use of CaCl2 and MgCl2 as cell permeabilizing additives also increased gram-negative bacteria susceptibility to indigo. PMID:25764449

  17. Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects.

    PubMed

    Wang, Shunhao; Riedinger, Andreas; Li, Hongbo; Fu, Changhui; Liu, Huiyu; Li, Linlin; Liu, Tianlong; Tan, Longfei; Barthel, Markus J; Pugliese, Giammarino; De Donato, Francesco; Scotto D'Abbusco, Marco; Meng, Xianwei; Manna, Liberato; Meng, Huan; Pellegrino, Teresa

    2015-02-24

    Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics. PMID:25603353

  18. 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.

  19. Photodynamic therapy with fullerenes in vivo: reality or a dream?

    PubMed Central

    Sharma, Sulbha K; Chiang, Long Y; Hamblin, Michael R

    2012-01-01

    Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine. PMID:22122587

  20. 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

  1. Photodynamic inactivation of Gram-positive bacteria employing natural resources.

    PubMed

    Mamone, L; Di Venosa, G; Gándara, L; Sáenz, D; Vallecorsa, P; Schickinger, S; Rossetti, M V; Batlle, A; Buzzola, F; Casas, A

    2014-04-01

    The aim of this paper was to investigate a collection of plant extracts from Argentina as a source of new natural photosensitizers (PS) to be used in Photodynamic Inactivation (PDI) of bacteria. A collection of plants were screened for phototoxicity upon the Gram-positive species Staphylococcus epidermidis. Three extracts turned out to be photoactive: Solanum verbascifolium flower, Tecoma stans flower and Cissus verticillata root. Upon exposure to a light dose of 55J/cm(2), they induced 4, 2 and 3logs decrease in bacterial survival, respectively. Photochemical characterisation of S. verbascifolium extract was carried out. PDI reaction was dependent mainly on singlet oxygen and to a lesser extent, on hydroxyl radicals, through type II and I reactions. Photodegradation experiments revealed that the active principle of the extract was not particularly photolabile. It is noticeable that S. verbascifolium -PDI was more efficient under sunlight as compared to artificial light (total eradication vs. 4 logs decrease upon 120min of sunlight). The balance between oxidant and antioxidant compounds is likely to be masking or unmasking potential PS of plant extracts, but employing the crude extract, the level of photoactivity of S. verbascifolium is similar to some artificial PS upon exposure to sunlight, demonstrating that natural resources can be employed in PDI of bacteria. PMID:24705374

  2. Optimization of photodynamic therapy with chlorins for chest malignancies

    NASA Astrophysics Data System (ADS)

    Ris, Hans-Beat; Giger, Andreas; Im Hof, Vinzenz; Althaus, Ulrich; Altermatt, Hans J.

    1996-01-01

    Photodynamic therapy (PDT) following surgical tumor resection is leading to improved local tumor control and might be useful for selected intrathoracic malignancies. However, optimal tumor selectivity of PDT is mandatory to avoid injury of adjacent normal tissues. (1) PDT was applied on human tumor xenografts (malignant mesothelioma, squamous cell carcinoma of the neck, adenocarcinoma of the colon). M-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derived mTHPC (MD-mTHPC) were administered i.p. The tumor and normal tissue of the hind leg were irradiated with 652 nm laser-light. Drug and light doses and drug-light intervals were varied. The extent of necrosis was assessed histologically. (2) Intrathoracic PDT was performed in minipigs with drug-light doses optimized in nude mice. After administration of the sensitizers i.v., intrathoracic structures were irradiated and analyzed histologically. The tumor selectivity of PDT increased in the xenograft model by: (1) choosing an appropriate drug light interval; (2) decreasing the drug dose while increasing the light dose; and (3) applying MD-mTHPC instead of mTHPC. In the minipig model, the extent of injury of intrathoracic structures was equally related to modulation of treatment conditions. The modification of chlorins and the modulation of the drug-light conditions improved the tissue selectivity of PDT. Nevertheless, further methodological optimizations are prerequisites for clinical use of PDT, especially for intraoperative application in thoracic surgery.

  3. 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

  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. Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile

    PubMed Central

    Pye, Hayley; Kohoutova, Darina; Mosse, Charles A.; Yahioglu, Gokhan; Stamati, Ioanna; Deonarain, Mahendra; Battah, Sinan; Ready, Derren; Allan, Elaine; Mullany, Peter; Lovat, Laurence B.

    2015-01-01

    Background Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections. Methods PACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29. Results Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT. Conclusion This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon. PMID:26313448

  6. Necrosis prediction of photodynamic therapy applied to skin disorders

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-02-01

    The great selectivity and the lack of side effects of Photodynamic Therapy make it more advantageous than radiotherapy or chemotherapy. The application of PDT to skin diseases is particularly appropriate, due to the accessibility of this tissue. Common disorders like nonmelanoma skin cancer, that includes basocelullar or squamous cell carcinomas, can be treated with PDT. Conventional procedures, like surgery or radiotherapy, are not so efficient and do not, in general, obtain the same favourable results. PDT in dermatology medical praxis uses fixed protocols depending on the photosensitizer and the optical source used. These protocols are usually provided by the photosensitizer laboratory, and every lesion is treated with the same parameters. In this work we present a photo-chemical model of PDT applied to skin disorders treated with topical photosensitizers. Optical propagation inside the tissue is calculated by means of a 3D diffusion equation, solved via a finite difference numerical method. The photosensitizer degradation or photobleaching is taken into account, as the drug looses efficiency with the irradiation time. With these data the necrosis area is estimated, so this model could be used as a predictive tool to adjust the optical power and exposition time for the particular disease under treatment.

  7. Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.

    PubMed

    Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R

    2005-07-01

    The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence. PMID:15986057

  8. Cationic porphyrin derivatives for application in photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Prack McCormick, Bárbara P.; Florencia Pansa, M.; Milla Sanabria, Laura N.; Carvalho, Carla M. B.; Faustino, M. Amparo F.; Neves, Maria Graça P. M. S.; Cavaleiro, José A. S.; Rumie Vittar, Natalia B.; Rivarola, Viviana A.

    2014-04-01

    Current studies in photodynamic therapy (PDT) against cancer are focused on the development of new photosensitizers (PSs), with higher phototoxic action. The aim of this study was to compare the therapeutic efficiency of tri-cationic meso-substituted porphyrin derivatives (Tri-Py+-Me-PF, Tri-Py+-Me-Ph, Tri-Py+-Me-CO2Me and Tri-Py+-Me-CO2H) with the well-known tetra-cationic T4PM. The phototoxic action of these derivatives was assessed in human colon adenocarcinoma cells by cell viability, intracellular localization and nuclear morphology analysis. In the experimental conditions used we determined that after light activation -PF, -Ph and -CO2Me cause a more significant decline of cell viability compared to -CO2H and T4PM. These results suggest that the nature of the peripheral substituent influences the extent of cell photodamage. Moreover, we have demonstrated that PS concentration, physicochemical properties and further light activation determine the PDT response. All porphyrins were clearly localized as a punctuated pattern in the cytoplasm of the cells, and the PDT scheme resulted in apoptotic cell death after 3 h post-PDT. The tri-cationic porphyrin derivatives Tri-Py+-Me-PF, Tri-Py+-Me-Ph and Tri-Py+-Me-CO2Me showed a promising ability, making them good photosensitizer candidates for oncological PDT.

  9. New stable synthetic bacteriochlorins for photodynamic therapy of melanoma

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Huang, Ying-Ying; Janjua, Sahar; Zhiyentayev, Timur; Ruzié, Christian; Borbas, K. Eszter; Fan, Dazhong; Krayer, Michael; Balasubramanian, Thiagarajan; Yang, Eun Kyung; Kee, Hooi Ling; Holten, Dewey; Lindsey, Jonathan S.; Hamblin, Michael R.

    2009-06-01

    Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and has afforded highly encouraging results in skin cancers such as basal cell carcinoma. However, pigmented melanoma remains a notable exception from the range of tumors treated by PDT largely due to the fact that melanin has high absorption of light in wavelength regions where most clinically approved photosensitizers (PS) absorb light (600-690 nm). Moreover, melanoma cells sequester exogenous molecules including photosensitizers inside melanosomes. The aforementioned drawbacks of the clinically used PS have motivated us to search for new classes of PS with improved spectral properties, such as bacteriochlorins (BC) to be used in PDT of melanoma. To overcome the PDT-resistance mechanisms of melanoma, particularly the high optical absorption of melanin, three near-infrared (NIR) absorbing synthetic stable BC were used in PDT treatment of melanoma. Dose and fluence dependent cell killing, intracellular localization (particularly in melanosomes), and correlation between the melanin level and cell death were examined. Intracellular melanosomes are ruptured after illumination as shown by electron microscopy. The best in vitro performing BC were tested upon delivery in micellar nanoparticles against a mouse pigmented melanoma. Two of the BC were effective at significantly lower concentrations (<0.5 μM) than common photosensitizers in present use.

  10. Polymeric micelles encapsulating photosensitizer: structure/photodynamic therapy efficiency relation.

    PubMed

    Gibot, Laure; Lemelle, Arnaud; Till, Ugo; Moukarzel, Béatrice; Mingotaud, Anne-Françoise; Pimienta, Véronique; Saint-Aguet, Pascale; Rols, Marie-Pierre; Gaucher, Mireille; Violleau, Frédéric; Chassenieux, Christophe; Vicendo, Patricia

    2014-04-14

    Various polymeric micelles were formed from amphiphilic block copolymers, namely, poly(ethyleneoxide-b-ε-caprolactone), poly(ethyleneoxide-b-d,l-lactide), and poly(ethyleneoxide-b-styrene). The micelles were characterized by static and dynamic light scattering, electron microscopy, and asymmetrical flow field-flow fractionation. They all displayed a similar size close to 20 nm. The influence of the chemical structure of the block copolymers on the stability upon dilution of the polymeric micelles was investigated to assess their relevance as carriers for nanomedicine. In the same manner, the stability upon aging was assessed by FRET experiments under various experimental conditions (alone or in the presence of blood proteins). In all cases, a good stability over 48 h for all systems was encountered, with PDLLA copolymer-based systems being the first to release their load slowly. The cytotoxicity and photocytotoxicity of the carriers were examined with or without their load. Lastly, the photodynamic activity was assessed in the presence of pheophorbide a as photosensitizer on 2D and 3D tumor cell culture models, which revealed activity differences between the 2D and 3D systems. PMID:24552313

  11. Stimulation of anti-tumor immunity by photodynamic therapy

    PubMed Central

    Mroz, Pawel; Hashmi, Javad T; Huang, Ying-Ying; Lange, Norbert; Hamblin, Michael R

    2011-01-01

    Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a ‘danger signal’ to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy. PMID:21162652

  12. 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-).

  13. 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

  14. 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.

  15. Selective photosensitizer delivery into plasma membrane for effective photodynamic therapy.

    PubMed

    Kim, Jiyoung; Santos, Olavo Amorim; Park, Ji-Ho

    2014-10-10

    Subcellular localization of photosensitizers (PSs) determines the therapeutic efficacy in the photodynamic therapy. However, among the subcellular compartments, there has been little effort to deliver the PSs selectively into the plasma membrane and examine the phototherapeutic efficacy of membrane-localized PSs. Here, we developed a liposomal delivery system to localize the hydrophobic PSs selectively into the plasma membrane. The membrane fusogenic liposomes (MFLs), the membrane of which is engineered to fuse with the plasma membrane, was prepared for the membrane localization of PSs. The phototherapeutic efficacy of cells treated with ZnPc-loaded MFLs was superior over that of cells treated with ZnPc-loaded non-fusogenic liposomes, which is the conventional liposomal formulation that delivers the PSs into the intracellular compartments via endocytosis. The membrane localization of ZnPc molecules led to rapid membrane disruption upon irradiation and subsequent necrosis-like cell death. The membrane-localized generation of reactive oxygen species in the cells treated with ZnPc-loaded MFLs was likely to account for the effective disruption of plasma membrane. Thus, this work provides a novel delivery method to localize the PSs selectively into the plasma membrane with the enhanced phototherapeutic efficacy. PMID:24892975

  16. Volume changes of human endothelial cells induced by photodynamic treatment

    NASA Astrophysics Data System (ADS)

    Leunig, Andreas; Staub, Frank; Plesnila, Nick; Peters, Jurgen; Feyh, Jens; Gutmann, Ralph; Goetz, Alwin E.

    1996-01-01

    Photodynamic therapy (PDT) has shown promising results in treatment of malignant tumors. However, the mechanisms leading to tumor destruction during PDT are still not completely understood. In addition to effects on the microcirculation, damage to cellular structures has been observed following exposure of cells to PDT. A phenomenon preceding these events might possibly be cell swelling. We therefore studied the influence of treatment with Photofrin (PF) and laser light on volume changes and cell viability of endothelial cells. Endothelial cells were obtained from human umbilical cord veins (HUVEC) by an adaption of the method of Maruyama (1963). After subcultivation the cells were harvested and transferred as a cell suspension into a specially designed incubation chamber. Cells received either PF in concentrations of 1.5 or 3.0 (mu) g/ml and laser illumination (630 nm; 40 mW/cm2, 4 Joule), PF alone, or laser treatment only. Following start of PF incubation and after phototreatment cell samples were taken for volume measurements using flow cytometry and for studies of cellular morphology using scanning electron microscopy. Simultaneously, cell viability was monitored by the trypan blue exclusion test and colorimetric MTT assay. (abstract truncated)

  17. Exploiting apoptosis in photodynamic therapy: is it possible?

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar D.

    2003-06-01

    Glioblastoma Multiforme is the most common form of malignant brain tumors and accounts for approximately 25% of all primary brain tumors. Only 5% of these patients survive longer than 2 years. The standard form of treatment is radiation therapy and surgery if the site is accessible. Different forms of adjuvant chemotherapy have been largely proven unsuccessful. Another form of adjuvant therapy, Photodynamic Therapy (PDT), has undergone preliminary trials showing some promising results but at the cost of increased side effects like rise in intracranial blood pressure and neurological deficiency. Apoptotic cell kill used as a biological treatment endpoint can possibly ameliorate these side effects. This study evaluates the significance of apoptotic cell death in the 9L rat gliosarcoma using the aminolevulinic acid (ALA) induced endogenous photosensitizer Protophorphyrin IX (PpIX). A strong influence of drug incubation time with cell kill was observed. The percentage of apoptotic cell death was less than 10% for 2 and 4 hours incubation times and irradiation times ensuring up to 70 and 80% cell kill respectively. Accumulation of PpIX in the mitochondria and cytoplasm was quantified by confocal fluorescence microscopy showing a linear relationship of PpIX fluorescence with concentration. The possibility of an in vitro threshold in the PDT dose is discussed, above which cell repair mechanisms may become exhausted. In conclusion for the range of parameters investigated, apoptotic cell kill may be hard to exploit therapeutically in this tumor model.

  18. Photodynamic therapy on the ultrastructure of glioma cell

    NASA Astrophysics Data System (ADS)

    Hu, Shaoshan; Zhang, Ruyou; Zheng, Yongri

    2005-07-01

    OBJECTIVE :the main purpose of this experiment was to study the change of C6 glioma cells' ultrastructure treated by photodynamic therapy(PDT), observe the change of morphology METHOD :Make the model of rat glioma by transplanted C6 glioma cells into caudate nucleus,treated the glioma rat by PDT after two weeks. Observed the difference of subcellular structure before and after PDT by electron microscope. RESULT : Apoptosis and necrosis can be seen after treated by PDT in the C6 glioma, basal membrance damaged ,number of cellular organ of endothelial cell of blood capillary declined,tight junction of endothelial cell lengthen and the gap enlarge. The PDT has slightly effect on the nomorl rat"s subcellular structue. CONCLUSION: PDT can induce the apoptosis and necrosis of C6 glioma cell. The damage of the ultramicrostructure of mitochondria and endoplasmic reticulum was the foundmentol of the change. PDT initiate the damage of BBB of the C6 glioma cell and weeken the function、and makes it a useful way of treating the glioma combained with chemotherapy.

  19. Structural evolution of the methane cation in subfemtosecond photodynamics.

    PubMed

    Mondal, T; Varandas, A J C

    2015-07-01

    An ab initio quantum dynamics study has been performed to explore the structural rearrangement of ground state CH4 (+) in subfemtosecond resolved photodynamics. The method utilizes time-dependent wave-packet propagation on the X˜(2)T2 electronic manifold of the title cation in full dimensionality, including nonadiabatic coupling of the three electronic sheets. Good agreement is obtained with recent experiments [Baker et al., Science 312, 424 (2006)] which use high-order harmonic generation to probe the attosecond proton dynamics. The novel results provide direct theoretical support of the observations while unravelling the underlying details. With the geometrical changes obtained by calculating the expectation values of the nuclear coordinates as a function of time, the structural evolution is predicted to begin through activation of the totally symmetric a1 and doubly degenerate e modes. While the former retains the original Td symmetry of the cation, the Jahn-Teller active e mode conducts it to a D2d structure. At ∼1.85 fs, the intermediate D2d structure is further predicted to rearrange to local C2v minimum geometry via Jahn-Teller active bending vibrations of t2 symmetry. PMID:26156480

  20. Structural evolution of the methane cation in subfemtosecond photodynamics

    NASA Astrophysics Data System (ADS)

    Mondal, T.; Varandas, A. J. C.

    2015-07-01

    An ab initio quantum dynamics study has been performed to explore the structural rearrangement of ground state CH 4+ in subfemtosecond resolved photodynamics. The method utilizes time-dependent wave-packet propagation on the X ˜ 2 T 2 electronic manifold of the title cation in full dimensionality, including nonadiabatic coupling of the three electronic sheets. Good agreement is obtained with recent experiments [Baker et al., Science 312, 424 (2006)] which use high-order harmonic generation to probe the attosecond proton dynamics. The novel results provide direct theoretical support of the observations while unravelling the underlying details. With the geometrical changes obtained by calculating the expectation values of the nuclear coordinates as a function of time, the structural evolution is predicted to begin through activation of the totally symmetric a1 and doubly degenerate e modes. While the former retains the original Td symmetry of the cation, the Jahn-Teller active e mode conducts it to a D2d structure. At ˜1.85 fs, the intermediate D2d structure is further predicted to rearrange to local C2v minimum geometry via Jahn-Teller active bending vibrations of t2 symmetry.

  1. Effect of photodynamic therapy with verteporfin on tumor blood flow

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Pogue, Brian W.; Goodwin, Isak A.; O'Hara, Julia A.; Wilmot, Carmen M.; Hutchins, John E.; Hoopes, P. J.; Hasan, Tayyaba

    2003-06-01

    The success of photodynamic therapy with verteporfin is partially determined by the pharmacokinetic distribution of the sensitizer at the time of treatment. In this study tumor blood flow changes in the RIF-1 murine tumor model and tumor resopnse using the regrowth assay were measured, comparing two different intervals between drug and light administration. Blood flow measurements were taken with a laser Doppler system monitoring continuously over 1 hour and periodically up to 6 hours after treatment. Treatment after the longer interval caused significantly less flow decrease, to only 50% of the initial flow in 6 h. Hoechst staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors after the longer time interval, the regrowth rate was not signifincalty different from that of the control, indicating that only the 15-min interval group caused serious damage to the vascular bed of the tumor. These studies support the hypothesis that temporal pharmacokinetic changes in the photosensitizer distribution between the tumor parenchyma and blood vessels can significantly alter the mechanism of tumor targeting during therapy.

  2. Effects of fluence rate on cytoxicity during photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sitnik, Theresa M.; Henderson, Barbara W.

    1997-05-01

    Production of 1O2 during PDT may be limited as a consequence of tissue oxygen depletion by the photodynamic process. This may in turn limit cytotoxicity during PDT. One possible way of controlling oxygen consumption during treatment is through modification of fluence rate. We have studied the impact of fluence rate on tumor oxygenation and direct PDT cytotoxicity using the RIF murine tumor and the photosensitizer Photofrin. Both fluence rates caused an acute decrease in tumor pO2 to severely hypoxic levels. With 150 mW/cm2 light median pO2 remained low during prolonged exposure, while with 30 mW/cm2 light median pO2 values recovered to above control levels. When tumors treated with 135 J/cm2 at each fluence rate were tested for cell survival in a clonogenic assay, 30 mW/cm2 significantly decreased both cell clonogenicity and plating efficiency compared to light-only controls. Slight but insignificant decreases were found with 150 mW/cm2. During in vitro PDT the fluence rate of light delivery had no effect on cell survival. In summary, we have found that low fluence rate improves tumor oxygenation and direct cell effects during PDT.

  3. Photodynamic therapy induces an immune response against a bacterial pathogen

    PubMed Central

    Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Garcia-Diaz, Maria; Chang, Julie; Morimoto, Yuji; Hamblin, Michael R

    2012-01-01

    Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin®. PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease. PMID:22882222

  4. A Multireference Configuration Interaction Study of the Photodynamics of Nitroethylene

    PubMed Central

    2014-01-01

    Extended multireference configuration interaction with singles and doubles (MR-CISD) calculations of nitroethylene (H2C=CHNO2) were carried out to investigate the photodynamical deactivation paths to the ground state. The ground (S0) and the first five valence excited electronic states (S1–S5) were investigated. In the first step, vertical excitations and potential energy curves for CH2 and NO2 torsions and CH2 out-of-plane bending starting from the ground state geometry were computed. Afterward, five conical intersections, one between each pair of adjacent states, were located. The vertical calculations mostly confirm the previous assignment of experimental spectrum and theoretical results using lower-level calculations. The conical intersections have as main features the torsion of the CH2 moiety, different distortions of the NO2 group and CC, CN, and NO bond stretchings. In these conical intersections, the NO2 group plays an important role, also seen in excited state investigations of other nitro molecules. Based on the conical intersections found, a photochemical nonradiative deactivation process after a π–π* excitation to the bright S5 state is proposed. In particular, the possibility of NO2 release in the ground state, an important property in nitro explosives, was found to be possible. PMID:25158277

  5. A robotic multi-channel platform for interstitial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sharikova, Anna V.; Finlay, Jarod C.; Dimofte, Andreea; Zhu, Timothy C.

    2013-03-01

    A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel's motor had an optical encoder for position feedback, with resolution of 0.05 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials.

  6. Usefulness of Photodynamic Therapy in the Management of Onychomycosis.

    PubMed

    Robres, P; Aspiroz, C; Rezusta, A; Gilaberte, Y

    2015-12-01

    Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (λ=630 nm, 37 J.cm(-2)). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment. PMID:26427737

  7. 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.

  8. Mechanisms of tumor destruction caused by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhou, Chuannong

    2005-07-01

    Photodynamic therapy is a relatively new treatment modality and is becoming widely accepted as a standard treatment of a variety of solid tumors. This includes palliative treatments for advanced or obstructive cancers in many organs as well as a curative treatment for some early cancers and pre-cancerous lesions. It has been approved by health authorities in a number of countries in America, Europe and Asia [1]. PDT is a procedure requiring 3 elements: photosensitizer, light and oxygen [2]. The typical technique involves an intravenous administration of a photosensitizing agent, which is preferentially accumulated or retained in tumor tissue, followed by irradiation of the tumor area with light of appropriate wavelength. In the presence of oxygen it generates highly reactive and cytotoxic molecular species, in particular, singlet oxygen (1O2), which may oxidize various bio-molecules and finally leading to cell death and tumor destruction [3]. The most widely used photosensitizer in clinical treatment of cancers is Photofrin (porfimer sodium), and most widely used light sources are lasers of various types, in recent years preferentially, diode laser, which emits a red light of 630 nm wavelength.

  9. In vitro studies of the antiherpetic effect of photodynamic therapy.

    PubMed

    Zverev, V V; Makarov, O V; Khashukoeva, A Z; Svitich, O A; Dobrokhotova, Y E; Markova, E A; Labginov, P A; Khlinova, S A; Shulenina, E A; Gankovskaya, L V

    2016-07-01

    The number of viral infection cases in the Department of Gynecology and Obstetrics has tended to increase over last few years. Viruses form herpesvirus and cytomegalovirus families are associated with an increased risk for recurrent pregnancy loss. Photodynamic therapy (PDT) is a promising new approach to treat viral infections in which viral particles are inactivated. It exhibits great therapeutic potential, particularly among this group of patients. This study examined the use of PDT to treat herpesvirus infection (HVI) using an in vitro model. In this study, we used the Vero сell lineage as a suitable model of HVI, strains of HSV-1 (strain VR-3) and HSV-2 (strain MS) obtained from The National Virus Collection (London, UK), the photosensitizer Fotoditazine (Veta-Grand, Russia), an AFS physiotherapeutic device (Polironic Corporation, Russia). Laser light irradiation and the photosensitizer had different cytotoxic effects on the Vero cell cultures depending on the doses used. The optimal laser light and photosensitizer doses were determined. PDT had an antiviral effect on an in vitro model of HVI in cell culture. PDT has been shown to be effective treatment for HVI in vitro, leading to a reliable decrease of viral titer. PMID:27003896

  10. Light dosimetry calculations for esophageal photodynamic therapy using porfimer sodium

    NASA Astrophysics Data System (ADS)

    Jones, Linda R.; Preyer, Norris W., Jr.; Davis, Monica A.; Grimes, Carson; Edling, Kristie; Holdgate, Nicholas; Wallace, Michael B.; Wolfsen, Herbert C.

    2006-02-01

    Background: Photodynamic therapy using porfimer sodium (Ps-PDT) is approved for use in patients with Barrett's highgrade dysplasia and esophageal carcinoma. Ps-PDT light dosimetry, however, is critically important to treatment outcomes since insufficient ablation results in residual dysplasia and carcinoma while excessive treatment results in stricture formation. Aim: The aim of this study was to model esophageal PDT with optical absorption and scattering coefficients derived from an ex-vivo porcine multilayer esophagus model. Methods: Optical coefficients were derived for the mucosal and muscle layers of normal pig esophagus. The mucosal layer (mucosa, muscularis mucosa and submucosa) was separated from the muscle layer. Diffuse reflectance and transmittance were measured with an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were determined with the inverse adding doubling method. (Table not available in abstract, see pdf of paper) Multilayer Monte Carlo simulation and single-layer mathematical dosimetry equations were employed to model esophageal PDT with the derived coefficients. Porfimer sodium addition was modeled with an increase in both absorption and scattering. Depth of injury, assumed to require a threshold light dose, was estimated for various light doses commonly used in clinical practice. Depth of injury was then compared to clinical outcomes reported in the literature for various light doses.

  11. Dynamic Inhomogeneity in the Photodynamics of Cyanobacterial Phytochrome Cph1

    PubMed Central

    2015-01-01

    Phytochromes are widespread red/far-red photosensory proteins well known as critical regulators of photomorphogenesis in plants. It is often assumed that natural selection would have optimized the light sensing efficiency of phytochromes to minimize nonproductive photochemical deexcitation pathways. Surprisingly, the quantum efficiency for the forward Pr-to-Pfr photoconversion of phytochromes seldom exceeds 15%, a value very much lower than that of animal rhodopsins. Exploiting ultrafast excitation wavelength- and temperature-dependent transient absorption spectroscopy, we resolve multiple pathways within the ultrafast photodynamics of the N-terminal PAS-GAF-PHY photosensory core module of cyanobacterial phytochrome Cph1 (termed Cph1Δ) that are primarily responsible for the overall low quantum efficiency. This inhomogeneity primarily reflects a long-lived fluorescent subpopulation that exists in equilibrium with a spectrally distinct, photoactive subpopulation. The fluorescent subpopulation is favored at elevated temperatures, resulting in anomalous excited-state dynamics (slower kinetics at higher temperatures). The spectral and kinetic behavior of the fluorescent subpopulation strongly resembles that of the photochemically compromised and highly fluorescent Y176H variant of Cph1Δ. We present an integrated, heterogeneous model for Cph1Δ that is based on the observed transient and static spectroscopic signals. Understanding the molecular basis for this dynamic inhomogeneity holds potential for rational design of efficient phytochrome-based fluorescent and photoswitchable probes. PMID:24742290

  12. Photodynamic inactivation of biofilm building microorganisms by photoactive facade paints.

    PubMed

    Preuß, Annegret; Bornhütter, Tobias; Färber, Alexander; Schaller, Christian; Röder, Beate

    2016-07-01

    This study was performed as a proof of concept for singlet oxygen generating facade paint as an alternative to conventional biocide containing facade paint for the prevention of biofilm growth on outdoor walls. Biofilms on outdoor walls cause esthetic problems and economic damage. Therefore facade paints often contain biocides. However commercially available biocides may have a series of adverse effects on living organisms as well as harmful environmental effects. Furthermore, biocides are increasingly designed to be more effective and are environmentally persistent. Thus, an eco-friendly and non-harmful to human health alternative to conventional biocides in wall color is strongly recommended. The well-known photosensitizer 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine (TMPyP) was used as an additive in a commercially available facade paint. The generation of singlet molecular oxygen was shown using time resolved 2D measurements of the singlet oxygen luminescence. The photodynamic activity of the photosensitizer in the facade paint was demonstrated by phototoxicity tests with defined mold fungi and a mixture of microorganisms harvested from native outdoor biofilms as model organisms. It was proven in general that it is possible to inhibit the growth of biofilm forming microorganisms growing on solid wall paint surfaces by the cationic photosensitizer TMPyP added to the facade paint using daylight conditions for illumination in 12h light and dark cycles. PMID:27101275

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

    PubMed

    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

  14. Photodynamic therapy of oral Candida infection in a mouse model.

    PubMed

    Freire, Fernanda; Ferraresi, Cleber; Jorge, Antonio Olavo C; Hamblin, Michael R

    2016-06-01

    Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis. PMID:27074245

  15. Photodynamic therapy in early esophageal squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

    1995-03-01

    From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

  16. Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling

    PubMed Central

    Wang, Ken Kang-Hsin; Finlay, Jarod C.; Busch, Theresa M.; Hahn, Stephen M.; Zhu, Timothy C.

    2011-01-01

    Singlet oxygen (1O2) is the major cytotoxic agent responsible for cell killing for type-II photodynamic therapy (PDT). An empirical four-parameter macroscopic model is proposed to calculate the “apparent reacted 1O2 concentration”, [1O2]rx, as a clinical PDT dosimetry quantity. This model incorporates light diffusion equation and a set of PDT kinetics equations, which can be applied in any clinical treatment geometry. We demonstrate that by introducing a fitting quantity “apparent singlet oxygen threshold concentration” [1O2]rx,sd, it is feasible to determine the model parameters by fitting the computed [1O2]rx to the Photofrin-mediated PDT-induced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [1O2]rx,sd, we expect to use this model as an explicit dosimetry to assess PDT treatment outcome for a specific photosensitizer in an in vivo environment. The results also provide evidence that the [1O2]rx, because it takes into account the oxygen consumption (or light fluence rate) effect, can be a better predictor of PDT outcome than the PDT dose defined as the energy absorbed by the photosensitizer, which is proportional to the product of photosensitizer concentration and light fluence. PMID:20222102

  17. Extended rhodamine photosensitizers for photodynamic therapy of cancer cells.

    PubMed

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

    2016-09-01

    Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). PMID:27246858

  18. Pheophorbides as photosensitizers for the photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Tanielian, Charles; Wolff, Christian; Kobayashi, Masami

    1995-01-01

    Quantum yields for formation of singlet molecular oxygen have been measured for sodium pheophorbides (Na-Phdes) a and b in aqueous and non-aqueous media. Measurements have been made for both steady-state and pulsed laser excitation with the resultant singlet molecular oxygen being detected by photo-oxygenation reactions or time-resolved luminescence spectroscopy, respectively. Singlet oxygen production sensitized by Na-Phdes a or b is insignificant in aqueous media but occurs with a good efficiency in organic solvents. Plasmid DNA is efficiently photocleaved by Na-Phdes a and b in the absence of oxygen as well as in the presence of oxygen. Fluorescence microscopic observation shows a rapid incorporation of Na-Phde a into nuclei, mitochondria, and lysosome of human oral mucosa cells. In contrast Na-Phde b is incorporated only into the plasma membrane. The photodynamic activity of these pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures.

  19. 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.

  20. Chemical modification of normal tissue damage induced by photodynamic therapy.

    PubMed Central

    Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

    1996-01-01

    One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

  1. Application of long-circulating liposomes to cancer photodynamic therapy.

    PubMed

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S

    1997-06-01

    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT. PMID:9212988

  2. Effects of photodynamic therapy on Enterococcus faecalis biofilms.

    PubMed

    López-Jiménez, L; Fusté, E; Martínez-Garriga, B; Arnabat-Domínguez, J; Vinuesa, T; Viñas, M

    2015-07-01

    Microbial biofilms are involved in almost all infectious pathologies of the oral cavity. This has led to the search for novel therapies specifically aimed at biofilm elimination. In this study, we used atomic force microscopy (AFM) to visualize injuries and to determine surface roughness, as well as confocal laser scanning microscopy (CLSM) to enumerate live and dead bacterial cells, to determine the effects of photodynamic therapy (PDT) on Enterococcus faecalis biofilms. The AFM images showed that PDT consisting of methylene blue and a 670-nm diode laser (output power 280 mW during 30 s) or toluidine blue and a 628-nm LED light (output power 1000 mW during 30 s) induced severe damage, including cell lysis, to E. faecalis biofilms, with the former also causing an important increase in surface roughness. These observations were confirmed by the increase in dead cells determined using CLSM. Our results highlight the potential of PDT as a promising method to achieve successful oral disinfection. PMID:25917515

  3. Light distribution in the endometrium during photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Madsen, Sten; Svaasand, Lars O.; Fehr, Mathias K.; Tadir, Yona; Ngo, Phat; Tromberg, Bruce J.

    1995-01-01

    Hysterectomy is the most common major operation performed in the United States with dysfunctional uterine bleeding being a major indication. Endometrial destruction by photodynamic therapy (PDT) has been suggested as a possible alternative to invasive surgical procedures for abnormal uterine bleeding due to benign changes. Effective destruction of the endometrium during PDT requires a sufficient amount of light to be delivered to the entire endometrium in a reasonable time. To satisfy these criteria, we have developed a trifurcated optical applicator consisting of three cylindrical diffusing fibers. The applicator was inserted into freshly excised, intact human uteri and the optical distribution was measured with an isotropic fiber probe at various locations in the uterus. The results were in good agreement with the predictions of a mathematical model based on diffusion theory. The results indicate that irradiation of the endometrium by the trifurcated applicator can destroy tissue to a depth of 4 mm given an optical power of 100 mW per cm of diffusing tip (100 mW/cm) for an exposure time of less than 20 minutes.

  4. Innovative approaches of clinical photodynamic therapy combined with immunotherapy

    NASA Astrophysics Data System (ADS)

    Huang, Zheng

    2006-02-01

    Photodynamic therapy (PDT) is a clinically approved new treatment modality. It has been used for treatment of non-malignant and malignant diseases. Over the last decade its clinical application has gained increasing acceptance around the world after regulatory approvals. PDT offers various treatment options in cancer management and has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. Recently, its application has also been expanded to solid tumors. However, its efficacy for the treatment of malignant tumors remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the direct local cytotoxicity, PDT can induce host immune responses, which may further enhance the therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, the antitumor efficacy of PDT might also be enhanced through an effective immunoadjuvant to further expand its usefulness for a possible control of distant metastases. Recent clinical data also indicate that improved clinical outcomes are seen in the combination of PDT and immunomodulation therapy for non-malignant disease. This review will summarize recent progress in developing innovative approaches of PDT combined with immunotherapy for non-malignant and malignant diseases.

  5. 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.

  6. Treatment of canine oral squamous cell carcinomas with photodynamic therapy

    PubMed Central

    McCaw, D L; Pope, E R; Payne, J T; West, M K; Tompson, R V; Tate, D

    2000-01-01

    Eleven dogs with naturally occurring oral squamous cell carcinomas were treated with photodynamic therapy (PDT) using Photochlor (HPPH) as the photosensitizer. The largest length of the tumours measured in a two-dimensional plane ranged from 0.9 to 6.8 cm. Seven of the tumours invaded underlying bone as determined by radiograph appearance. Photochlor was injected intravenously at a dose of 0.3 mg kg–1. Forty-eight hours later the tumours were treated. Tumours with a surface to base depth of greater than 1 cm were surgically reduced to less than 1 cm. Irradiation with 665 nm light with an energy density of 100 J cm–2was administered. Eight dogs were considered cured with no tumour recurrence for at least 17 months after treatment. Local treatment of oral squamous cell carcinomas with PDT appears to give results similar to those obtained with surgical removal of large portions of the mandible or maxilla. The cosmetic results with PDT are superior to those of radical surgical removal. The new sensitizer, Photochlor, appears effective for oral squamous carcinomas with results similar to those reported for other sensitizers. © 2000 Cancer Research Campaign PMID:10755404

  7. 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

  8. 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.

  9. New approaches to photodynamic therapy of tumors with Al phthalocyanine

    NASA Astrophysics Data System (ADS)

    Vakoulovskaya, Elena G.; Chental, V. V.; Kuvshinov, Yury P.; Poddubny, Boris K.

    1999-12-01

    The aim of the study was to determine the efficacy of photodynamic therapy (PDT) of tumors of different localization and histology with new photosensitizer aluminum sulfonated phthalocyanine (Photosense, Russia). PDT have been provided in 106 patients with different tumors. The initial dose (2.0 - 2.5 mg/kg) of PHS was significantly reduced till 0.5 - 0.8 mg/kg during clinical trials because of phototoxicity. The results of PDT, 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. Efficacy of PDT depended on tumor size and it's histological type. Using low doses of PHS we've reduced the phototoxicity of sensitizer with the same direct effectiveness of treatment. Undesirable changes in plasma content of antioxidants by means of high pressure liquid chromatography 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.

  10. Photodynamic treatment of lens epithelial cells for cataract surgery

    NASA Astrophysics Data System (ADS)

    Lingua, Robert W.; Parel, Jean-Marie A.; Simon, Gabriel; Li, Kam

    1991-06-01

    Photodynamic therapy (PDT) eiiploying Dihematopor*iyrin ethers (DHE) (Photofrin II) at pharmacologic lvels, has been denonstrate3 to kill rabbit lens epithelial cells, in vivo. This in vitro study, reports on the minimal necessary parameters for rabbit lens epithelial cell death. Explants of rabbit lenses were incubated in various concentrations of DHE (1O,, 100, 500, 1000 ug/ml) for 1, 2, or 5 minutes. 30 to 120 Joules/an of collimated 514.5 nm Argon laser light re delivered to the locier concentrations of 10, 50, and 100 ug,'ml DHE treated cells. One hundre1 fifteen explants were treated, in all. Higher concentrations of DHE alone (500 and 1000 ug/ml) were sufficient to induce cellular swelling. Lower concentrations required light for cellular effect. Trypan blue staining revealed cell death at these minimal pa9ieters: DHE 50 ug/ml, incubation 1 minute, 514.5 r Argon light 1.0 Watt/an for 30 sec (30 Joules) . In future studies, these rameters will be tested in vivo, for their ability to eliminate lens epithelial proliferation after cataract surgery.

  11. Probing the Photodynamics of Rhodopsins with Reduced Retinal Chromophores.

    PubMed

    Manathunga, Madushanka; Yang, Xuchun; Luk, Hoi Ling; Gozem, Samer; Frutos, Luis Manuel; Valentini, Alessio; Ferrè, Nicolas; Olivucci, Massimo

    2016-02-01

    While the light-induced population dynamics of different photoresponsive proteins has been investigated spectroscopically, systematic computational studies have not yet been possible due to the phenomenally high cost of suitable high level quantum chemical methods and the need of propagating hundreds, if not thousands, of nonadiabatic trajectories. Here we explore the possibility of studying the photodynamics of rhodopsins by constructing and investigating quantum mechanics/molecular mechanics (QM/MM) models featuring reduced retinal chromophores. In order to do so we use the sensory rhodopsin found in the cyanobacterium Anabaena PCC7120 (ASR) as a benchmark system. We find that the basic mechanistic features associated with the excited state dynamics of ASR QM/MM models are reproduced using models incorporating a minimal (i.e., three double-bond) chromophore. Furthermore, we show that ensembles of nonadiabatic ASR trajectories computed using the same abridged models replicate, at both the CASPT2 and CASSCF levels of theory, the trends in spectroscopy and lifetimes estimated using unabridged models and observed experimentally at room temperature. We conclude that a further expansion of these studies may lead to low-cost QM/MM rhodopsin models that may be used as effective tools in high-throughput in silico mutant screening. PMID:26640959

  12. Characterizing light propagation in bone for photodynamic therapy of osteosarcoma

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent M.; Gustafson, Scott B.; Jacques, Steven L.

    2009-02-01

    This work aims at characterizing how light propagates through bone in order to efficiently guide treatment of osteosarcoma with photodynamic therapy (PDT). Optical properties of various bone tissues need to be characterized in order to have a working model of light propagation in bone. Bone tissues of particular interest include cortical bone, red and yellow marrow, cancellous bone, and bone cancers themselves. With adequate knowledge of optical properties of osseous tissues, light dosimetry can determine how best to deliver adequate light to achieve phototoxic effects within bone. An optical fiber source-collector pair is used for diffuse reflectance spectroscopic measurements in order to determine the scattering and absorption properties of bone tissues. Native absorbers of interest at visible and near-IR wavelengths include water and oxygenated and deoxygenated hemoglobin. A cylindrically symmetric Monte Carlo model is then used, incorporating these results, in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect in PDT.

  13. 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.

  14. 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.

  15. Photodynamic therapy: An adjunct to conventional root canal disinfection strategies.

    PubMed

    Singh, Shipra; Nagpal, Rajni; Manuja, Naveen; Tyagi, Sashi Prabha

    2015-08-01

    Although chemical-based root canal disinfectants are important to reduce microbial loads and remove infected smear layer from root dentin, they have only a limited ability to eliminate biofilm bacteria, especially from root complexities. This paper explores the novel photodynamic therapy (PDT) for antimicrobial disinfection of root canals. The combination of an effective photosensitizer, the appropriate wavelength of light and ambient oxygen is the key factor in PDT. PDT uses a specific wavelength of light to activate a non-toxic dye (photosensitizer), leading to the formation of reactive oxygen species. These reactive oxygen molecules can damage bacterial proteins, membrane lipids and nucleic acids, which promote bacterial cell death. In, addition PDT may enhance cross-linking of collagen fibrils in the dentin matrix and thereby improving dentin stability. The concept of PDT is plausible and could foster new therapy concepts for endodontics. The available knowledge should enable and encourage steps forward into more clinical-oriented research and development. This article discusses PDT as related to root canal disinfection, including its components, mechanism of action, reviews the current endodontic literature and also highlights the shortcomings and advancements in PDT techniques. PMID:25404404

  16. Photonanomedicine: a convergence of photodynamic therapy and nanotechnology.

    PubMed

    Obaid, Girgis; Broekgaarden, Mans; Bulin, Anne-Laure; Huang, Huang-Chiao; Kuriakose, Jerrin; Liu, Joyce; Hasan, Tayyaba

    2016-07-01

    As clinical nanomedicine has emerged over the past two decades, phototherapeutic advancements using nanotechnology have also evolved and impacted disease management. Because of unique features attributable to the light activation process of molecules, photonanomedicine (PNM) holds significant promise as a personalized, image-guided therapeutic approach for cancer and non-cancer pathologies. The convergence of advanced photochemical therapies such as photodynamic therapy (PDT) and imaging modalities with sophisticated nanotechnologies is enabling the ongoing evolution of fundamental PNM formulations, such as Visudyne®, into progressive forward-looking platforms that integrate theranostics (therapeutics and diagnostics), molecular selectivity, the spatiotemporally controlled release of synergistic therapeutics, along with regulated, sustained drug dosing. Considering that the envisioned goal of these integrated platforms is proving to be realistic, this review will discuss how PNM has evolved over the years as a preclinical and clinical amalgamation of nanotechnology with PDT. The encouraging investigations that emphasize the potent synergy between photochemistry and nanotherapeutics, in addition to the growing realization of the value of these multi-faceted theranostic nanoplatforms, will assist in driving PNM formulations into mainstream oncological clinical practice as a necessary tool in the medical armamentarium. PMID:27328309

  17. 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.

  18. 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

  19. Photodynamic Effects of Radachlorin® on Cervical Cancer Cells

    PubMed Central

    Bae, Su-Mi; Kim, Yong-Wook; Lee, Joon-Mo; Namkoong, Sung-Eun; Han, Sei-Jun; Kim, Jong-Ki; Lee, Chang-Hee; Chun, Heung-Jae; Jin, Hyun-Sun

    2004-01-01

    Purpose Photodynamic therapy (PDT) is a novel treatment modality, which produces local tissue necrosis with laser light following the prior administration of a photosensitizing agent. Radachlorin® has recently been shown to be a promising PDT sensitizer. In order to elucidate the antitumor effects of PDT using Radachlorin® on cervical cancer, growth inhibition studies on a HPV-associated tumor cell line, TC-1 cells in vitro and animals with an established TC-1 tumor in vivo were determined. Materials and Methods TC-1 tumor cells were exposed to various concentrations of Radachlorin® and PDT, with irradiation of 12.5 or 25 J/cm2 at an irradiance of 20 mW/cm2 using a Won-PDT D662 laser at 662 nm in vitro. C57BL/6 mice with TC-1 tumor were injected with Radachlorin® via different routes and treated with PDT in vivo. A growth suppression study was then used to evaluate the effects at various time points after PDT. Results The results showed that irradiation of TC-1 tumor cells in the presence of Radachlorin® induced significant cell growth inhibition. Animals with established TC-1 tumors exhibited significantly smaller tumor sizes over time when treated with Radachlorin® and irradiation. Conclusion PDT after the application of Radachlorin® appears to be effective against TC-1 tumors both in vitro and in vivo. PMID:20368834

  20. Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Xu, Yu; Shi, Zhenzhi; Zhang, Ling'e.; Brown, Eric Michael Bratsolias; Wu, Aiguo

    2016-06-01

    Layered bismuth oxyhalide nanomaterials have received much more interest as promising photocatalysts because of their unique layered structures and high photocatalytic performance, which can be used as potential inorganic photosensitizers in tumor photodynamic therapy (PDT). In recent years, photocatalytic materials have been widely used in PDT and photothermal therapy (PTT) as inorganic photosensitizers. This investigation focuses on applying layered bismuth oxyhalide nanomaterials toward cancer PDT, an application that has never been reported so far. The results of our study indicate that the efficiency of UV-triggered PDT was highest when using BiOCl nanoplates followed by BiOCl nanosheets, and then TiO2. Of particular interest is the fact that layered BiOCl nanomaterials showed excellent PDT effects under low nanomaterial dose (20 μg mL-1) and low UV dose (2.2 mW cm-2 for 10 min) conditions, while TiO2 showed almost no therapeutic effect under the same parameters. BiOCl nanoplates and nanosheets have shown excellent performance and an extensive range of applications in PDT.

  1. Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy.

    PubMed

    Xu, Yu; Shi, Zhenzhi; Zhang, Ling'e; Brown, Eric Michael Bratsolias; Wu, Aiguo

    2016-07-01

    Layered bismuth oxyhalide nanomaterials have received much more interest as promising photocatalysts because of their unique layered structures and high photocatalytic performance, which can be used as potential inorganic photosensitizers in tumor photodynamic therapy (PDT). In recent years, photocatalytic materials have been widely used in PDT and photothermal therapy (PTT) as inorganic photosensitizers. This investigation focuses on applying layered bismuth oxyhalide nanomaterials toward cancer PDT, an application that has never been reported so far. The results of our study indicate that the efficiency of UV-triggered PDT was highest when using BiOCl nanoplates followed by BiOCl nanosheets, and then TiO2. Of particular interest is the fact that layered BiOCl nanomaterials showed excellent PDT effects under low nanomaterial dose (20 μg mL(-1)) and low UV dose (2.2 mW cm(-2) for 10 min) conditions, while TiO2 showed almost no therapeutic effect under the same parameters. BiOCl nanoplates and nanosheets have shown excellent performance and an extensive range of applications in PDT. PMID:26287933

  2. Combined laser and photodynamic treatment in extensive purulent wounds

    NASA Astrophysics Data System (ADS)

    Solovieva, A. B.; Tolstih, P. I.; Melik-Nubarov, N. S.; Zhientaev, T. M.; Kuleshov, I. G.; Glagolev, N. N.; Ivanov, A. V.; Karahanov, G. I.; Tolstih, M. P.; Timashev, P. S.

    2010-05-01

    Recently, photodynamic therapy (PDT) has been used for the treatment of festering wounds and trophic ulcers. An important advantage of PDT is its ability to affect bacterial cultures that are resistant to antibiotics. However the use of PDT alone does not usually guarantee a stable antiseptic effect and cannot prevent an external infection of wounds and burns. In this work attention is focused on the healing of the extensive soft tissues wounds with combined laser therapy (LT) and PDT treatment. At the first stage of this process festering tissues (for example spacious purulent wounds with area more than 100 cm2) were illuminated with high-energy laser beam (with power 20 W) in continues routine. The second stage involves “softer” PDT affect, which along with the completion stages of destruction pathological cells, stimulating the process of wound granulation and epithelization. Also, according to our previous results, photosensitizer (photoditazin) is introduced inside the wound with different amphiphilic polymers for increasing the PDT efficacy.

  3. Photosensitizer absorption coefficient modeling and necrosis prediction during Photodynamic Therapy.

    PubMed

    Salas-García, Irene; Fanjul-Vélez, Félix; Arce-Diego, José Luis

    2012-09-01

    The development of accurate predictive models for Photodynamic Therapy (PDT) has emerged as a valuable tool to adjust the current therapy dosimetry to get an optimal treatment response, and definitely to establish new personal protocols. Several attempts have been made in this way, although the influence of the photosensitizer depletion on the optical parameters has not been taken into account so far. We present a first approach to predict the spatio-temporal variation of the photosensitizer absorption coefficient during PDT applied to dermatological diseases, taking into account the photobleaching of a topical photosensitizer. This permits us to obtain the photons density absorbed by the photosensitizer molecules as the treatment progresses and to determine necrosis maps to estimate the short term therapeutic effects in the target tissue. The model presented also takes into account an inhomogeneous initial photosensitizer distribution, light propagation in biological media and the evolution of the molecular concentrations of different components involved in the photochemical reactions. The obtained results allow to investigate how the photosensitizer depletion during the photochemical reactions affects light absorption by the photosensitizer molecules as the optical radiation propagates through the target tissue, and estimate the necrotic tumor area progression under different treatment conditions. PMID:22704663

  4. Dynamic inhomogeneity in the photodynamics of cyanobacterial phytochrome Cph1.

    PubMed

    Kim, Peter W; Rockwell, Nathan C; Martin, Shelley S; Lagarias, J Clark; Larsen, Delmar S

    2014-05-01

    Phytochromes are widespread red/far-red photosensory proteins well known as critical regulators of photomorphogenesis in plants. It is often assumed that natural selection would have optimized the light sensing efficiency of phytochromes to minimize nonproductive photochemical deexcitation pathways. Surprisingly, the quantum efficiency for the forward Pr-to-Pfr photoconversion of phytochromes seldom exceeds 15%, a value very much lower than that of animal rhodopsins. Exploiting ultrafast excitation wavelength- and temperature-dependent transient absorption spectroscopy, we resolve multiple pathways within the ultrafast photodynamics of the N-terminal PAS-GAF-PHY photosensory core module of cyanobacterial phytochrome Cph1 (termed Cph1Δ) that are primarily responsible for the overall low quantum efficiency. This inhomogeneity primarily reflects a long-lived fluorescent subpopulation that exists in equilibrium with a spectrally distinct, photoactive subpopulation. The fluorescent subpopulation is favored at elevated temperatures, resulting in anomalous excited-state dynamics (slower kinetics at higher temperatures). The spectral and kinetic behavior of the fluorescent subpopulation strongly resembles that of the photochemically compromised and highly fluorescent Y176H variant of Cph1Δ. We present an integrated, heterogeneous model for Cph1Δ that is based on the observed transient and static spectroscopic signals. Understanding the molecular basis for this dynamic inhomogeneity holds potential for rational design of efficient phytochrome-based fluorescent and photoswitchable probes. PMID:24742290

  5. 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.

  6. 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.

  7. 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.

  8. Photonanomedicine: a convergence of photodynamic therapy and nanotechnology

    NASA Astrophysics Data System (ADS)

    Obaid, Girgis; Broekgaarden, Mans; Bulin, Anne-Laure; Huang, Huang-Chiao; Kuriakose, Jerrin; Liu, Joyce; Hasan, Tayyaba

    2016-06-01

    As clinical nanomedicine has emerged over the past two decades, phototherapeutic advancements using nanotechnology have also evolved and impacted disease management. Because of unique features attributable to the light activation process of molecules, photonanomedicine (PNM) holds significant promise as a personalized, image-guided therapeutic approach for cancer and non-cancer pathologies. The convergence of advanced photochemical therapies such as photodynamic therapy (PDT) and imaging modalities with sophisticated nanotechnologies is enabling the ongoing evolution of fundamental PNM formulations, such as Visudyne®, into progressive forward-looking platforms that integrate theranostics (therapeutics and diagnostics), molecular selectivity, the spatiotemporally controlled release of synergistic therapeutics, along with regulated, sustained drug dosing. Considering that the envisioned goal of these integrated platforms is proving to be realistic, this review will discuss how PNM has evolved over the years as a preclinical and clinical amalgamation of nanotechnology with PDT. The encouraging investigations that emphasize the potent synergy between photochemistry and nanotherapeutics, in addition to the growing realization of the value of these multi-faceted theranostic nanoplatforms, will assist in driving PNM formulations into mainstream oncological clinical practice as a necessary tool in the medical armamentarium.

  9. Photodynamic Efficiency: From Molecular Photochemistry to Cell Death

    PubMed Central

    Bacellar, Isabel O. L.; Tsubone, Tayana M.; Pavani, Christiane; Baptista, Mauricio S.

    2015-01-01

    Photodynamic therapy (PDT) is a clinical modality used to treat cancer and infectious diseases. The main agent is the photosensitizer (PS), which is excited by light and converted to a triplet excited state. This latter species leads to the formation of singlet oxygen and radicals that oxidize biomolecules. The main motivation for this review is to suggest alternatives for achieving high-efficiency PDT protocols, by taking advantage of knowledge on the chemical and biological processes taking place during and after photosensitization. We defend that in order to obtain specific mechanisms of cell death and maximize PDT efficiency, PSes should oxidize specific molecular targets. We consider the role of subcellular localization, how PS photochemistry and photophysics can change according to its nanoenvironment, and how can all these trigger specific cell death mechanisms. We propose that in order to develop PSes that will cause a breakthrough enhancement in the efficiency of PDT, researchers should first consider tissue and intracellular localization, instead of trying to maximize singlet oxygen quantum yields in in vitro tests. In addition to this, we also indicate many open questions and challenges remaining in this field, hoping to encourage future research. PMID:26334268

  10. Photodynamic inactivation of somatic frog nerve ex vivo

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Seliverstov, George A.; Akchurin, George G.; Kudryashova, Svetlana Y.

    2004-06-01

    New techniques research mechanisms of photdynamic reactions at somatic frog nerve was approved. Dosimetry PDT with minimum time resolution ~1ms determined by changing the amplitude of compound action potential of somatic frog nerve. Light-induced inactivation of dynamic response of somatic frog nerve on electrical pulsed excitation was study ex vivo. The light-sensitive dyes: methylene blue (Mb), Indocianin green and eryhtrocin-B has been used on photodynamic induced inactivation of the processes generation nerve pulses. Inactivation of consequence action potential of somatic frog nerve using excitation of electical pulsed was achieved by irradiation with He-Ne laser light in a red spectral region (λ=633 nm, power level 2-20 mW), diode laser (λ=805 nm, P<0.1-1 W/cm2) in the case of Indocianin green and YAG:Nd laser (λ=532 nm, P~1mW) for eryhtrocin-B. It was discovered that methylene blue, Indocainine green and erytrocin-B decrease of the amplitude compound action potential of the ensemble neurons. The possible cell death mechanism was connected with damage of the sodium potassium adenosine triphosphatase (K-Na ATP) active transport which decrease of amplitude of compound action potential and decrease lifetime ionic channel of membrane nerve.

  11. 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.

  12. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  13. Development and optimization of a diode laser for photodynamic therapy

    PubMed Central

    Lim, Hyun Soo

    2011-01-01

    Background and Aims: This study demonstrated the development of a laser system for cancer treatment with photodynamic therapy (PDT) based on a 635 nm laser diode. In order to optimize efficacy in PDT, the ideal laser system should deliver a homogeneous nondivergent light energy with a variable spot size and specific wavelength at a stable output power. Materials and Methods: We developed a digital laser beam controller using the constant current method to protect the laser diode resonator from the current spikes and other fluctuations, and electrical faults. To improve the PDT effects, the laser system should deliver stable laser energy in continuous wave (CW), burst mode and super burst mode, with variable irradiation times depending on the tumor type and condition. Results and Comments: The experimental results showed the diode laser system described herein was eminently suitable for PDT. The laser beam was homogeneous without diverging and the output power increased stably and in a linear manner from 10 mW to 1500 mW according to the increasing input current. Variation between the set and delivered output was less than 7%. Conclusions: The diode laser system developed by the author for use in PDT was compact, user-friendly, and delivered a stable and easily adjustable output power at a specific wavelength and user-set emission modes. PMID:24155529

  14. Photodynamic therapy and fluorescent diagnostics of breast cancer

    NASA Astrophysics Data System (ADS)

    Vakulovskaya, Elena G.; Letyagin, Victor P.; Umnova, Loubov V.; Vorozhcsov, Georgiu N.; Philinov, Victor

    2004-06-01

    Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using Photosense have been provided in 26 patients with breast cancer (BC) and in 108 patients with skin metastases of BC. In 22 patients with T1-T2N0M0 primary tumor PDT was preoperative treatment, with radical mastectomy 7-10 days after PDT. 4 patients had residual tumor after radiotherapy. FD was fulfilled with spectranalyser. We used semiconductive laser for PDT-λ=672+2nm, P=1,5 W, interstitial irradiation 2-24 hours after PS injection in light dose 150-200 J/cm3 in patients with primary tumor and multiple surface irradiations (1-4) with interval 24-48 hours and total light dose 400-600 J/cm2 for metastases. Partial regression of tumor with pathomorphosis of 2-4 degree has been found in 23 cases in first group. Treating metastases we had overall response rate of 86,9% with complete response (CR) in 51,5% and partial response in 35,4%. In a year after PDT in 52 patients with CR we had CR in 36,6%, local recurrences in 23,1%, progression (distant [lung or bone] metastasis) in 40,4% of cases. Our experience show pronounced efficacy of FD for detecting tumor borders and PDT for treating BC as preoperative modality and as palliation in cases of recurrencies.

  15. Solid state lasers for photodynamic therapy of malignant neoplasm

    NASA Astrophysics Data System (ADS)

    Khulugurov, Vitaliy M.; Ivanov, Nikolai; Kim, Byoung-Chul; Mayorov, Alexander; Bordzilovsky, Dnitri; Masycheva, Valentina; Danilenko, Elena; Chung, Moon-Kwan

    2002-05-01

    This work demonstrates the possibility of treating animals with malignant neoplasms using 608 nm of laser radiation by means of photodynamic therapy (PDT). The intracavity transformation of the Nd:YAP main radiation 1079 nm was Raman converted in barium nitrate crystal, and the Stokes frequency (1216 nm) was doubled using KTP or RTA crystals. The LiF or Cr:YAG crystals are used for the Q-switch. The radiation parameters were obtained at 100 Hz pump repetition frequency. The average power at 608-nm radiation with LiF and KTP was 700 mW at multimode generation. The 3-6 single 10-15 ns pulses were generated during one cycle of pumping. The doubling efficiency with RTA was two times more than with KTP. The cells of Ehrlich adenocarcinoma (0.1 ml) were implanted in hind thighs of ICR white non-imbred mice. Photosensitizer HpD was i.v. administered in a dose of 10 mg/kg. Ten animals were treated (2 as a control). There was a 9-30% decrease in the tumor growth depending on the irradiation dose. The better result (30%) was for the 200 J/cm2 dose radiation. These results show the possibility of using all solid state lasers with wavelength of 608 nm for PDT.

  16. Photodynamic therapy for lung cancer and malignant pleural mesothelioma.

    PubMed

    Simone, Charles B; Cengel, Keith A

    2014-12-01

    Photodynamic therapy (PDT) is a form of non-ionizing radiation therapy that uses a drug, called a photosensitizer, combined with light to produce singlet oxygen ((1)O2) that can exert anti-cancer activity through apoptotic, necrotic, or autophagic tumor cell death. PDT is increasingly being used to treat thoracic malignancies. For early-stage non-small cell lung cancer (NSCLC), PDT is primarily employed as an endobronchial therapy to definitively treat endobronchial or roentgenographically occult tumors. Similarly, patients with multiple primary lung cancers may be definitively treated with PDT. For advanced or metastatic NSCLC and small cell lung cancer (SCLC), PDT is primarily employed to palliate symptoms from obstructing endobronchial lesions causing airway compromise or hemoptysis. PDT can be used in advanced NSCLC to attempt to increase operability or to reduce the extent of operation intervention required, and selectively to treat pleural dissemination intraoperatively following macroscopically complete surgical resection. Intraoperative PDT can be safely combined with macroscopically complete surgical resection and other treatment modalities for malignant pleural mesothelioma (MPM) to improve local control and prolong survival. This report reviews the mechanism of and rationale for using PDT to treat thoracic malignancies, details prospective and major retrospectives studies of PDT to treat NSCLC, SCLC, and MPM, and describes improvements in and future roles and directions of PDT. PMID:25499640

  17. Cell death mechanisms vary with photodynamic therapy dose and photosensitizer

    NASA Astrophysics Data System (ADS)

    He, Jin; Oleinick, Nancy L.

    1995-03-01

    Mouse lymphoma L5178Y-R cells respond to photodynamic therapy (PDT) by undergoing rapid apoptosis, which is induced by PDT-activated signal transduction initiating in the damaged cellular membranes. To relate the level of PDT damage and photosensitizer to the mechanism of cell death, apoptosis has been detected by agarose gel electrophoresis of fragmented DNA and quantified by flow cytometry of cells after staining with Hoechst33342 and propidium iodide, a technique which can distinguish between live, apoptotic, and necrotic cells. When the silicon phthalocyanine Pc 4 or Pc 12 served as photosensitizer, lethal doses (as defined by clonogenic assay) of PDT induced apoptosis in essentially all cells, whereas supralethal doses prevented the characteristic degradation of DNA into oligonucleosomal fragments. In contrast with aluminum phthalocyanine (AlPc) cells died by apoptosis after all doses studied. It appears that high PDT doses with Pc 4 or Pc 12 damage enzymes needed to carry out the program of apoptosis; the absence of this effect with AlPc suggests either a different intracellular location or different photocytotoxic mechanism for the two photosensitizers.

  18. Reduction of Endotracheal Tube Biofilms Using Antimicrobial Photodynamic Therapy

    PubMed Central

    Biel, Merrill A.; Sievert, Chet; Usacheva, Marina; Teichert, Matthew; Wedell, Eric; Loebel, Nicolas; Rose, Andreas; Zimmermann, Ron

    2011-01-01

    Background Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation with a mortality rate of 24 to 71%. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. The objective of this study was to demonstrate the safety and effectiveness of a non-invasive antimicrobial photodynamic therapy (aPDT) treatment method of eradicating antibiotic resistant biofilms from ET tubes in an in vitro model. Methods Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue (MB) photosensitizer and 664nm non-thermal activating light. Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction. Results The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% (p<0.05%) after a single treatment. Conclusions MB aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube. PMID:21987599

  19. Photodynamic therapy for diffuse choroidal hemangioma in a child with Sturge-Weber syndrome.

    PubMed

    Nugent, Ryan; Lee, Lawrence; Kwan, Anthony

    2015-04-01

    Sturge-Weber syndrome is a rare neurocutaneous disorder involving the leptomeninges, skin of the face, and, in 40% of cases, diffuse choroidal hemangioma. We report the case of a 6-year-old girl with Sturge-Weber syndrome and a large diffuse choroidal hemangioma with retinal detachment involving the majority of the retina. The patient underwent photodynamic therapy. The retinal detachment resolved completely within 3 months of treatment. This case represents the youngest patient in the literature to undergo successful treatment with photodynamic therapy for Sturge-Weber syndrome-associated diffuse choroidal hemangioma. PMID:25828818

  20. Analysis of superficial fluorescence patterns in nonmelanoma skin cancer during photodynamic therapy by a dosimetric model

    NASA Astrophysics Data System (ADS)

    Salas-García, I.; Fanjul-Vélez, F.; Arce-Diego, J. L.

    2016-03-01

    In this work the superficial fluorescence patterns in different nonmelanoma skin cancers and their photodynamic treatment response are analysed by a fluorescence based dosimetric model. Results show differences of even more than 50% in the fluorescence patterns as photodynamic therapy progresses depending on the malignant tissue type. They demonstrate the great relevance of the biological media as an additional dosimetric factor and contribute to the development of a future customized therapy with the assistance of dosimetric tools to interpret the fluorescence images obtained during the treatment monitoring and the differential photodiagnosis.

  1. 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.

  2. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part One of a Five-Part Series

    PubMed Central

    2008-01-01

    The utilization of aminolevulinic acid–photodynamic therapy in dermatology has steadily been on the rise since its introduction into our therapeutic armamentarium almost 10 years ago. Clinicians are realizing the continued benefits of this therapy from a therapeutic and cosmetic/aesthetic outcome. This was first seen in the treatment of nonhyperkeratotic actinic keratoses of the face and scalp where resolution of the actinic keratoses was achieved and a cosmetic improvement noted from the therapies. Clinicians are embracing photorejuvenation utilizing aminolevulinic acid–photodynamic therapy, which is reviewed in this article. PMID:21103321

  3. 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

  4. Photosensitizer anchored gold nanorods for targeted combinational photothermal and photodynamic therapy.

    PubMed

    Tham, Huijun Phoebe; Chen, Hongzhong; Tan, Yu Hui; Qu, Qiuyu; Sreejith, Sivaramapanicker; Zhao, Lingzhi; Venkatraman, Subbu S; Zhao, Yanli

    2016-07-01

    Silylated zinc phthalocyanine (ZnPc) was anchored onto silica-coated gold nanorods (AuNR) with retained local surface plasmon resonance (LSPR). Independent LSPR and singlet oxygen production of anchored ZnPc enhance the photothermal and photodynamic efficacy of the obtained AuNR-Si-ZnPc under NIR light excitation. AuNR-Si-ZnPc was further grafted with hyaluronic acid (HA). Since HA has selective targeting capability to CD44 antigens, the final hybrid could target cancer cells directly for synergistic photothermal and photodynamic therapy. PMID:27346609

  5. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine.

    PubMed

    Korbelik, Mladen; Banáth, Judit; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M; Bielawska, Alicja; Separovic, Duska

    2016-09-15

    Acid ceramidase has been identified as a promising target for cancer therapy. One of its most effective inhibitors, LCL521, was examined as adjuvant to photodynamic therapy (PDT) using mouse squamous cell carcinoma SCCVII model of head and neck cancer. Lethal effects of PDT, assessed by colony forming ability of in vitro treated SCCVII cells, were greatly enhanced when combined with 10 µM LCL521 treatment particularly when preceding PDT. When PDT-treated SCCVII cells are used to vaccinate SCCVII tumor-bearing mice (PDT vaccine protocol), adjuvant LCL521 treatment (75 mg/kg) resulted in a marked retardation of tumor growth. This effect can be attributed to the capacity of LCL521 to effectively restrict the activity of two main immunoregulatory cell populations (Tregs and myeloid-derived suppressor cells, MDSCs) that are known to hinder the efficacy of PDT vaccines. The therapeutic benefit with adjuvant LCL521 was also achieved with SCCVII tumors treated with standard PDT when using immunocompetent mice but not with immunodeficient hosts. The interaction of LCL521 with PDT-based antitumor mechanisms is dominated by immune system contribution that includes overriding the effects of immunoregulatory cells, but could also include a tacit contribution from boosting direct tumor cell kill. PMID:27136745

  6. Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Qin, Chenchen; Fei, Jinbo; Wang, Anhe; Yang, Yang; Li, Junbai

    2015-11-01

    To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular

  7. Multifunctionalized mesoporous silica nanoparticles for the in vitro treatment of retinoblastoma: Drug delivery, one and two-photon photodynamic therapy.

    PubMed

    Gary-Bobo, Magali; Mir, Youssef; Rouxel, Cédric; Brevet, David; Hocine, Ouahiba; Maynadier, Marie; Gallud, Audrey; Da Silva, Afitz; Mongin, Olivier; Blanchard-Desce, Mireille; Richeter, Sébastien; Loock, Bernard; Maillard, Philippe; Morère, Alain; Garcia, Marcel; Raehm, Laurence; Durand, Jean-Olivier

    2012-08-01

    In this work, we focused on mesoporous silica nanoparticles (MSN) for one photon excitated photodynamic therapy (OPE-PDT) combined with drug delivery and carbohydrate targeting applied on retinoblastoma, a rare disease of childhood. We demonstrate that bitherapy (camptothecin delivery and photodynamic therapy) performed with MSN on retinoblastoma cancer cells was efficient in inducing cancer cell death. Alternatively MSN designed for two-photon excited photodynamic therapy (TPE-PDT) were also studied and irradiation at low fluence efficiently killed retinoblastoma cancer cells. PMID:22569231

  8. Clinical effect of meso-tetrahydroxyphenylchlorine based photodynamic therapy in recurrent carcinoma of the ovary: preliminary results.

    PubMed

    Wierrani, F; Fiedler, D; Grin, W; Henry, M; Dienes, E; Gharehbaghi, K; Krammer, B; Grünberger, W

    1997-03-01

    This article addresses the use of meso-tetrahydroxyphenylchlorin-based photodynamic therapy (m-THPC-PDT) to treat recurrent gynaecologic malignancies of the ovary. Photodynamic therapy is an experimental approach in the treatment of neoplasms and results indicate it is a highly tissue selective, relatively simple intervention with few side effects, therefore reducing the overall burden on the patient. Of the three patients involved in the initial study, two were treated solely with photodynamic therapy by laparoscopy, and one underwent additional palliative debulking surgery of metastatic tumours. After a post-operative period of more than two years all three women remained free of relapses. PMID:9091020

  9. A high density FinFET one-time programmable cell with new intra-fin cell isolation for advanced system on chip applications

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Zheng; Yuan, Jo En; Peng, Ping Chun; Hsiao, Woan Yun; King, Ya-Chin; Lin, Chrong Jung

    2016-04-01

    A fully CMOS compatible one-time programmable (OTP) cell with a novel intra-fin cell isolation (IFCI) structure on a FinFET CMOS process has been proposed. The IFCI OTP cell utilizes the field-enhanced dielectric breakdown at fin corners to perform a fast and low-voltage program operation. Moreover, an ultrasmall intra-fin cell-to-cell isolation is firstly introduced to markedly shrink the cell size by eliminating the area-consuming spacing of fin-to-fin isolation. The IFCI FinFET OTP with fast program speed, excellent read disturb immunity, and reliable data retention is a promising solution for logic nonvolatile memory (NVM) technology in advanced CMOS nodes.

  10. A single poly-Si gate-all-around junctionless fin field-effect transistor for use in one-time programming nonvolatile memory

    PubMed Central

    2014-01-01

    This work demonstrates a feasible single poly-Si gate-all-around (GAA) junctionless fin field-effect transistor (JL-FinFET) for use in one-time programming (OTP) nonvolatile memory (NVM) applications. The advantages of this device include the simplicity of its use and the ease with which it can be embedded in Si wafer, glass, and flexible substrates. This device exhibits excellent retention, with a memory window maintained 2 V after 104 s. By extrapolation, 95% of the original charge can be stored for 10 years. In the future, this device will be applied to multi-layer Si ICs in fully functional systems on panels, active-matrix liquid-crystal displays, and three-dimensional (3D) stacked flash memory. PMID:25404873

  11. "Even a donation one time in your live will help...": the effect of the legitimizing paltry contribution technique on blood donation.

    PubMed

    Guéguen, Nicolas

    2013-12-01

    Previous research has found that the statement "Even a penny will help" incorporated in charity donation requests increases compliance. The present study analyzed the effectiveness of this technique using a novel solicitation and an intermediate delay between the statement and the actual execution of the requested act. University students were solicited to give blood during a special one-day drive. Solicitations were made through face-to-face interactions. Solicitors wore a tee-shirt on which the statement "Even a donation one time in your live will help..." was either present or not. Results show that more participants gave their blood when this statement appeared on the tee-shirt. PMID:23725982

  12. Effects of Repeated Screw Tightening on Implant Abutment Interfaces in Terms of Bacterial and Yeast Leakage in Vitro: One-Time Abutment Versus the Multiscrewing Technique.

    PubMed

    Calcaterra, Roberta; Di Girolamo, Michele; Mirisola, Concetta; Baggi, Luigi

    2016-01-01

    Screw loosening can damage the interfaces of implant components, resulting in susceptibility to contamination of the internal parts by microorganisms. The aim of this study was to investigate the impact of abutment screw retightening on the leakage of two different types of bacteria, Streptococcus sanguinis and Fusobacterium nucleatum, and of the yeast Candida albicans. Two types of implant-abutment systems with tube-in-tube interfaces were tested. Groups A and B each used a different type of system that consisted of 20 different pieces that were assembled according to the manufacturer's torque recommendations; four samples in each group were closed just one time, four samples three times, four samples five times, four samples seven times, and four samples nine times. The implants of groups A and B were contaminated with 0.1 μL of microbial solution just before being assembled for the last time to minimize the possibility of contamination. Results showed a direct correlation between the number of colony-forming units grown in the plates and the closing/opening cycles of the implant-abutment systems. Within the limitations of this study, the results indicate the possibility that repeated closing/opening cycles of the implant-abutment unit may influence bacterial/yeast leakage, most likely as a consequence of decreased precision of the coupling between the abutment and the internal part of the dental implant. These findings suggest that a one-time abutment technique may avoid microbiologic leakage in cases of implant-abutment systems with tube-in-tube interfaces. PMID:26901305

  13. 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

  14. Enlightening the impact of immunogenic cell death in photodynamic cancer therapy

    PubMed Central

    Galluzzi, Lorenzo; Kepp, Oliver; Kroemer, Guido

    2012-01-01

    EMBO J 31 5, 1062–1079 (2012); published online 01172012 In this issue of The EMBO Journal, Garg et al (2012) delineate a signalling pathway that leads to calreticulin (CRT) exposure and ATP release by cancer cells that succumb to photodynamic therapy (PTD), thereby providing fresh insights into the molecular regulation of immunogenic cell death (ICD). PMID:22252132

  15. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

    PubMed Central

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-01-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform. PMID:26987618

  16. Photodynamic therapy for treatment of AIDS-related mucocutaneous Kaposi's sarcoma (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1992-06-01

    Since 1975, Phase I/II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy (PDT) in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, in 1981 two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts to cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of mucocutaneous Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions (endothelial cell tumors); (2) a tumor- specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; (4) the potential for retreatment without increasing side effects; and (5) porphyrin-mediated photoinactivation of enveloped viruses. Herein presented are seven cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular mucocutaneous lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.

  17. 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.

  18. In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis.

    PubMed

    Pinto, Juliana Guerra; Fontana, Letícia Correa; de Oliveira, Marco Antonio; Kurachi, Cristina; Raniero, Leandro José; Ferreira-Strixino, Juliana

    2016-07-01

    Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm(2) at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed. PMID:27056699

  19. Photodynamic effect of hypericin after topical application in the ex ovo quail chorioallantoic membrane model.

    PubMed

    Čavarga, Ivan; Bilčík, Boris; Výboh, Pavel; Záškvarová, Monika; Chorvát, Dušan; Kasák, Peter; Mlkvý, Peter; Mateašík, Anton; Chorvátová, Alžbeta; Miškovský, Pavol

    2014-01-01

    Photosensitizing properties of hypericin are well known, and the chicken chorioallantoic membrane has previously been used to test photodynamic effects of hypericin and other substances. In our study the photodynamic effect of hypericin in the ex ovo quail chorioallantoic membrane model was evaluated. Steady-state and time-resolved fluorescence spectroscopy of hypericin solution in PEG-400 and its mixture in PBS was performed to assess and characterize the process of aggregation and disaggregation of hypericin during the drug formulation preparation. A therapeutical formulation (2 µg/g of embryo weight) was topically applied on CAM into the silicone ring. Hypericin was excited by diode laser with wavelength 405 nm, fluence rate 140 mW/cm2, and fluence 16.8 J/cm2. Hypericin in 100% PEG-400 exhibits typical fluorescence spectra with a maximum of about 600 nm, while hypericin 10% PEG-400 formulation exhibits almost no fluorescence. Time resolved spectra analysis showed fluorescence decay of hypericin in 100% PEG-400 solution with a mean lifetime of 5.1 ns and in 10% PEG 4.1 ns. Damage of quail chorioallantoic membrane vasculature after photodynamic therapy ranged from hemorrhage and vanishing of capillary vessels to thrombosis, lysis, and hemorrhage of larger vessels.The presented findings suggest that quail embryos can be used as a suitable model to test the effect of hypericin and other photodynamic compounds. PMID:24414308

  20. The Antimicrobial Photodynamic Therapy in the Treatment of Peri-Implantitis

    PubMed Central

    Libotte, Fabrizio; Sabatini, Silvia; Grassi, Felice Roberto

    2016-01-01

    Introduction. The aim of this study is to demonstrate the effectiveness of addition of the antimicrobial photodynamic therapy to the conventional approach in the treatment of peri-implantitis. Materials and Methods. Forty patients were randomly assigned to test or control groups. Patients were assessed at baseline and at six (T1), twelve (T2), and twenty-four (T3) weeks recording plaque index (PlI), probing pocket depth (PPD), and bleeding on probing (BOP); control group received conventional periodontal therapy, while test group received photodynamic therapy in addition to it. Result. Test group showed a 70% reduction in the plaque index values and a 60% reduction in PD values compared to the baseline. BOP and suppuration were not detectable. Control group showed a significative reduction in plaque index and PD. Discussion. Laser therapy has some advantages in comparison to traditional therapy, with faster and greater healing of the wound. Conclusion. Test group showed after 24 weeks a better value in terms of PPD, BOP, and PlI, with an average pocket depth value of 2 mm, if compared with control group (3 mm). Our results suggest that antimicrobial photodynamic therapy with diode laser and phenothiazine chloride represents a reliable adjunctive treatment to conventional therapy. Photodynamic therapy should, however, be considered a coadjuvant in the treatment of peri-implantitis associated with mechanical (scaling) and surgical (grafts) treatments. PMID:27429618

  1. A Simple Experiment to Show Photodynamic Inactivation of Bacteria on Surfaces

    ERIC Educational Resources Information Center

    Caminos, Daniel A.; Durantini, Edgardo N.

    2007-01-01

    New suitable approaches were investigated to visualize the photodynamic inactivation (PDI) of bacteria immobilized on agar surfaces. The PDI capacities of a cationic photosensitizer (5,10,15,20-tetra(4-N,N,N-trimethylammoniumphenyl)porphyrin) and an anionic photosensitizer (5,10,15,20-tetra(4-sulfonatophenyl)porphyrin) were analyzed on a typical…

  2. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy.

    PubMed

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-01-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform. PMID:26987618

  3. Antimicrobial Photodynamic Therapy to treat chemotherapy-induced oral lesions: Report of three cases.

    PubMed

    Rocha, Breno Amaral; Melo Filho, Mário Rodrigues; Simões, Alyne

    2016-03-01

    The development of Angular Cheilitis and the reactivation of Herpes Simplex Virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. The objective of the present manuscript is to report Antimicrobial Photodynamic Therapy as a treatment of infected oral lesions of patients submitted to chemotherapy. PMID:26222604

  4. Development of a device for photodynamic therapy of oral cavity mucous

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, Ilya S.; Tuchin, Valery V.; Ulyanov, Sergey S.

    1999-03-01

    The device, offered for reviewing, was designed and developed for photodynamic therapy of oral cavity mucous diseases and for laboratory experiments on the red light influence on the bacterial colonies in presence of a dye. The device has rather simple construction, it is cheap but convenience in use.

  5. Dual pH-responsive 5-aminolevulinic acid pseudopolyrotaxane prodrug micelles for enhanced photodynamic therapy.

    PubMed

    Tong, Hongxin; Wang, Yin; Li, Huan; Jin, Qiao; Ji, Jian

    2016-03-11

    Novel 5-aminolevulinic acid (ALA) pseudopolyrotaxane prodrug micelles with dual pH-responsive properties were prepared by the host-guest interaction of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG). The micelles exhibited pH dependent cellular uptake and pH-sensitive ALA release, enabling enhanced photodynamic therapy. PMID:26882232

  6. Hypericin-based photodynamic therapy: antitumor activity, accumulation potential, and induced cell death pathway

    NASA Astrophysics Data System (ADS)

    Luksiene, Zivile; Vaitkuviene, Aurelija

    2004-09-01

    In this study the main interest was focused on the to investigation the photodynamic efficacy of hypericin, three other photosensitizers and 5 aminolevulinic acid-induced protopofirin IX in their ability to block the growth of rather aggressive tumor - Ehrlich ascite carcinoma in mice as well as Reh cells in humans (B-leukemia). Hypericin was found to exhibit the highest phototoxicity and antitumor activity in treating Ehrlich ascite carcinoma. The different photosensitizers were ranked as follows: Hypericin > hematoporphyrin dimethyl ether > Photofrin II > meso-tetra (para-sulfophenyl)porphin > 5-aminolevulinic acid. The most important is that just after Hyp-based photodynamic therapy 75% of mice survived a 4 month-period, and no recurrence of tumor within this period was detected in 25% of the treated mice. The clear cut correlation observed between intracellular dye concentration in the tumor cells and efficiency of photodynamic therapy, supports the idea that the intracellular accumulation of the photosensitizer is one of the most important factors in determining the benefit of photodynamic therapy. Hence, the accumulation of the photosensitizer in the tumor cells should be considered as one of the prognostic factors for the determination of the therapeutic outcome. Eventually, one of the most significant result is that hypericin is effective photosensitizer for human B-leukemia cells and induces apoptosis after photosensitization.

  7. An acid-cleavable phthalocyanine tetramer as an activatable photosensitiser for photodynamic therapy.

    PubMed

    Chow, Sun Y S; Lo, Pui-Chi; Ng, Dennis K P

    2016-08-16

    An acetal-linked self-quenched zinc(ii) phthalocyanine tetramer has been prepared. In an acidic environment in phosphate buffered saline or inside tumour cells, the phthalocyanine units of the tetramer are separated thereby restoring the fluorescence emission and singlet oxygen production. This response enables this compound to serve as a promising activatable photosensitiser for photodynamic therapy. PMID:27396392

  8. Photodynamic Anticancer Activity of CoFe2O4 Nanoparticles Conjugated with Hematoporphyrin.

    PubMed

    Park, Bong Joo; Choi, Kyong-Hoon; Nam, Ki Chang; Min, Jeeeun; Lee, Kyu-Dong; Uhm, Han Sup; Choi, Eun Ha; Kim, Ho-Joong; Jung, Jin-Seung

    2015-10-01

    This work reports the synthesis and the characterization of water-soluble and biocompatible photosensitizer (PS)-conjugated magnetic nanoparticles composed of a cobalt ferrite (CoFe2O4) magnetic core coated with a biocompatible hematoporphyrin (HP) shell. The photo-functional cobalt ferrite magnetic nanoparticles (CoFe2O4@HP) were uniform in size, stable against PS leaching, and highly efficient in the photo-generation of cytotoxic singlet oxygen under visible light. With the CoFe2O4@HP, we acquired in vitro MR images of cancer cells (PC-3) and confirmed good biocompatibility of the CoFe2O4@HP in both normal and cancer cells. In addition, we confirmed the potential of the CoFe2O4@HP as an agent for photodynamic therapy (PDT) applications. The photodynamic anticancer activities in 25, 50, and 100 μg/mL of CoFe2O4@HP were measured and found to exceed 99% (99.0, 99.4, and 99.5%) (p < 0.002). The photodynamic anticancer activity was 81.8% (p < 0.003). From these results, we suggest that our CoFe2O4@HP can be used safely as a type of photodynamic cancer therapy with potential as a therapeutic agent having good biocompatibility. Moreover, these photo-functional magnetic nanoparticles are highly promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering. PMID:26726437

  9. 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

  10. 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

  11. 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.

  12. Photodynamic therapy for Acinetobacter baumannii burn infections in mice.

    PubMed

    Dai, Tianhong; Tegos, George P; Lu, Zongshun; Huang, Liyi; Zhiyentayev, Timur; Franklin, Michael J; Baer, David G; Hamblin, Michael R

    2009-09-01

    Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10(8) A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections. PMID:19564369

  13. 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.

  14. Photodynamic therapy for localized infections – state of the art

    PubMed Central

    Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R

    2009-01-01

    Photodynamic therapy (PDT) was discovered over one hundred years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However in recent years interest in the antimicrobial effects of PDT has revived and it has been proposed as a therapy for a large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance amongst many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a lack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical studies of PDT for viral papillomatosis lesions and for acne refer to its anti-microbial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase. PMID:19932449

  15. Epithelial-mesenchymal interaction during photodynamic therapy-induced photorejuvenation.

    PubMed

    Kim, Sue Kyung; Koo, Gi-Bang; Kim, You-Sun; Kim, You Chan

    2016-09-01

    Recently, several clinical studies reported that the photodynamic therapy (PDT) has photorejuvenation effects on the aged skin. Previously, our group introduced evidence of direct effect of PDT on cultured fibroblast (FB). PDT directly stimulated FBs and induced collagen synthesis through activation of extracellular signal-regulated kinase. In this study, we investigated indirect effect of PDT on the human dermal FB during photorejuvenation focused on the epithelial-mesenchymal interaction between keratinocyte (KC) and FB. The "low-level PDT" condition was used for PDT therapy to the cultured KC. Various kinds of cytokines in the supernatants of KC were evaluated by enzyme-linked immunosorbent assay. FBs were stimulated with the KC-conditioned medium (KCM) taken after PDT. The mRNA level of matrix metalloproteinases (MMPs), transforming growth factor (TGF)-β and collagen type Iα in the FB, was determined by real-time polymerase chain reaction. Clinical phtorejuvenation effect was also evaluated from nine patients who had PDT to treat actinic keratoses. Among the FB-stimulating cytokines, a significant elevation of interleukin (IL)-1α, IL-6, and tumor necrosis factor-α level in KCM was noted after PDT compared with controls. After stimulating FB with KCM, the mRNA of MMP-1 was decreased and the mRNA of collagen type Iα was increased compare to control. Clinically, fine wrinkles significantly reduced after PDT. However, coarse wrinkles were not recovered significantly. In conclusion, increased collagen synthesis may be mediated not only by direct effect of PDT on FB but also by indirect effect of PDT on FB through cytokines from KC, such as IL-1α, IL-6, and tumor necrosis factor-α. PMID:27383261

  16. Modulation of inflammatory response of wounds by antimicrobial photodynamic therapy

    PubMed Central

    Sharma, Mrinalini; Gupta, Pradeep Kumar

    2015-01-01

    Background and aims: Management of infections caused by Pseudomonas aeruginosa is becoming difficult due to the rapid emergence of multi-antibiotic resistant strains. Antimicrobial photodynamic therapy (APDT) has a lot of potential as an alternative approach for inactivation of antibiotic resistant bacteria. In this study we report results of our investigations on the effect of poly-L-lysine conjugate of chlorine p6 (pl-cp6) mediated APDT on the healing of P.aeruginosa infected wounds and the role of Nuclear Factor kappa B (NF-kB) induced inflammatory response in this process. Materials and method: Excisional wounds created in Swiss albino mice were infected with ∼107 colony forming units of P.aeruginosa. Mice with wounds were divided into three groups: 1) Uninfected, 2) Infected, untreated control (no light, no pl-cp6), 3) Infected, APDT. After 24 h of infection (day 1 post wounding), the wounds were subjected to APDT [pl-cp6 applied topically and exposed to red light (660 ± 25 nm) fluence of ∼ 60 J/cm2]. Subsequent to APDT, on day 2 and 5 post wounding (p.w), measurements were made on biochemical parameters of inflammation [toll like receptor-4 (TLR-4), NF-kB, Inteleukin (IL)-[1α, IL-β, and IL-2)] and cell proliferation [(fibroblast growth factor-2 (FGF-2), alkaline phosphatase (ALP)]. Results: In comparison with untreated control, while expression of TLR-4, NF-kB (p105 and p50), and proinflammatory interleukins (IL-1α, IL-1β,IL-2) were reduced in the infected wounds subjected to APDT, the levels of FGF-2 and ALP increased, on day 5 p.w. Conclusion: The measurements made on the inflammatory markers and cell proliferation markers suggest that APDT reduces inflammation caused by P.aeruginosa and promotes cell proliferation in wounds. PMID:26557735

  17. 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.

  18. Methylene blue mediated photodynamic therapy for resistant plaque psoriasis.

    PubMed

    Salah, Manal; Samy, Nevien; Fadel, Maha

    2009-01-01

    Topical treatment of resistant psoriatic plaque stage lesions may be difficult and the systemic therapies seem inappropriate. Therefore, a topical 0.1% methylene blue (MB) hydrogel was prepared and evaluated for percent drug content, drug uniformity, pH, rheological and organoleptic characters such as feel tackiness, grittiness sensation, and transparency in addition to release kinetics study in vitro. The efficiency of the photodynamic therapy (PDT) of MB photo-activated using 565 mW Light emitting diode (LED) 670 nm was evaluated in patients with resistant plaque psoriasis. The gel was evaluated in single blinded study. The patients were subjected to repeated sessions of irradiation, skin biopsies from each patient in the beginning and at the end of the sessions were taken for histopathological studies. Results showed the hydrogel was transparent nongritty and the drug uniformly dispersed with pH=7.2 and viscosity value=25.04 Pa. The drug content was found to be 99.4 +/- 0.15 %. Drug release was following zero order kinetics with rate constant K=0.348 +/- 0.01 and T(1/2) = 0.95 +/- 0.5 hours. Sixteen patients experienced complete clearance of their treated lesions. Skin appeared normal in color, texture, and pliability with no complications indicating the lack of skin sensitivity. Histopathological examinations showed nearly normal epidermis at the end of all sessions. The authors concluded that the prepared hydrogel was safe, stable, and very effective. The results are encouraging to accept MB as a photosensitizer for PDT and as a safe and effective method for treatment of selected cases of resistant localized psoriasis PMID:19180895

  19. 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.

  20. Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.

    PubMed

    Ferrario, A; Gomer, C J

    1990-02-01

    An unexpected high level of acute lethality has been documented following Photofrin II-mediated photodynamic therapy (PDT) treatments which were localized to the hind leg of normal and tumor-bearing mice. Doses of PDT which induced lethality (10 mg/kg Photofrin II, 200-500 J/cm2) were in the range of doses required to obtain murine tumor cures. The percentage of lethality was proportional to the total light dose but was inversely proportional to the dose rate of delivered light. Comparable levels of acute toxicity were observed in four pigmented mouse strains (C57BL/6J, C3H/HeJ, DBA/1, and DBA/2) and in two albino mouse strains (BALB/c and Swiss Webster). Decreased sensitivity to PDT-induced lethality was observed in two pigmented mouse strains (B10D2/OSN and B10D2/NSN). The administration of warfarin, aspirin, indomethacin, or antihistamine had significant protective effects in terms of decreasing PDT-induced lethality. However, injection of cobra venom factor (to deplete C3 and C5 of the complement system) did not alter the lethality mediated by PDT. Histological profiles obtained 24 h following PDT demonstrated vascular congestion in the liver, kidney, lung, and spleen. Significant decreases in removable blood volume, core temperature, and spleen weight were also observed within 24 h of localized PDT treatment. These results indicate that PDT-induced lethality is consistent with a traumatic shock syndrome and suggest that endogenous vasoactive mediators of shock such as prostaglandins, thromboxanes, and histamine are associated with the lethality induced by localized PDT in mice. PMID:2137023

  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. Tin Tungstate Nanoparticles: A Photosensitizer for Photodynamic Tumor Therapy.

    PubMed

    Seidl, Carmen; Ungelenk, Jan; Zittel, Eva; Bergfeldt, Thomas; Sleeman, Jonathan P; Schepers, Ute; Feldmann, Claus

    2016-03-22

    The nanoparticulate inorganic photosensitizer β-SnWO4 is suggested for photodynamic therapy (PDT) of near-surface tumors via reiterated 5 min blue-light LED illumination. β-SnWO4 nanoparticles are obtained via water-based synthesis and comprise excellent colloidal stability under physiological conditions and high biocompatibility at low material complexity. Antitumor and antimetastatic effects were investigated with a spontaneously metastasizing (4T1 cells) orthotopic breast cancer BALB/c mouse model. Besides protamine-functionalized β-SnWO4 (23 mg/kg of body weight, in PBS buffer), chemotherapeutic doxorubicin was used as positive control (2.5 mg/kg of body weight, in PBS buffer) and physiological saline (DPBS) as a negative control. After 21 days, treatment with β-SnWO4 resulted in a clearly inhibited growth of the primary tumor (all tumor volumes below 3 cm(3)) as compared to the doxorubicin and DPBS control groups (volumes up to 6 cm(3)). Histological evaluations of lymph nodes and lungs as well as the volume of ipsilateral lymph nodes show a remarkable antimetastatic effect being similar to chemotherapeutic doxorubicin but-according to blood counts-at significantly reduced side effects. On the basis of low material complexity, high cytotoxicity under blue-light LED illumination at low dark and long-term toxicity, β-SnWO4 can be an interesting addition to PDT and the treatment of near-surface tumors, including skin cancer, esophageal/gastric/colon tumors as well as certain types of breast cancer. PMID:26894966

  3. Two-photon excitation photodynamic therapy with Photofrin

    NASA Astrophysics Data System (ADS)

    Karotki, Aliaksandr; Khurana, Mamta; Lepock, James R.; Wilson, Brian C.

    2005-09-01

    Photodynamic therapy (PDT) based on simultaneous two-photon (2-γ) excitation has a potential advantage of highly targeted treatment by means of nonlinear localized photosensitizer excitation. One of the possible applications of 2-γ PDT is a treatment of exodus age-related macular degeneration where highly targeted excitation of photosensitizer in neovasculature is vital for reducing collateral damage to healthy surrounding tissue. To investigate effect of 2-γ PDT Photofrin was used as an archetypal photosensitizer. First, 2-γ absorption properties of Photofrin in the 750 - 900 nm excitation wavelength range were investigated. It was shown that above 800 nm 2-γ interaction was dominant mode of excitation. The 2-γ cross section of Photofrin was rather small and varied between 5 and 10 GM (1 GM = 10-50 cm4s/photon) in this wavelength range. Next, endothelial cells treated with Photofrin were used to model initial effect of 2-γ PDT on neovasculature. Ultrashort laser pulses provided by mode-locked Ti:sapphire laser (pulse duration at the sample 300 fs, repetition rate 90 MHz, mean laser power 10 mW, excitation wavelength 850 nm) were used for the excitation of the photosensitizer. Before 2-γ excitation of the Photofrin cells formed a single continuous sheet at the bottom of the well. The tightly focused laser light was scanned repeatedly over the cell layer. After irradiation the cell layer of the control cells stayed intact while cells treated with photofrin became clearly disrupted. The light doses required were high (6300 Jcm(-2) for ~ 50% killing), but 2-γ cytotoxicity was unequivocally demonstrated.

  4. 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.

  5. Hyaluronidase To Enhance Nanoparticle-Based Photodynamic Tumor Therapy.

    PubMed

    Gong, Hua; Chao, Yu; Xiang, Jian; Han, Xiao; Song, Guosheng; Feng, Liangzhu; Liu, Jingjing; Yang, Guangbao; Chen, Qian; Liu, Zhuang

    2016-04-13

    Photodynamic therapy (PDT) is considered as a safe and selective way to treat a wide range of cancers as well as nononcological disorders. However, as oxygen is required in the process of PDT, the hypoxic tumor microenvironment has largely limited the efficacy of PDT to treat tumors especially those with relatively large sizes. To this end, we uncover that hyaluronidase (HAase), which breaks down hyaluronan, a major component of extracellular matrix (ECM) in tumors, would be able to enhance the efficacy of nanoparticle-based PDT for in vivo cancer treatment. It is found that the administration of HAase would lead to the increase of tumor vessel densities and effective vascular areas, resulting in increased perfusion inside the tumor. As a result, the tumor uptake of nanomicelles covalently linked with chlorine e6 (NM-Ce6) would be increased by ∼2 folds due to the improved "enhanced permeability and retention" (EPR) effect, while the tumor oxygenation level also shows a remarkable increase, effectively relieving the hypoxia state inside the tumor. Those effects taken together offer significant benefits in greatly improving the efficacy of PDT delivered by nanoparticles. Taking advantage of the effective migration of HAase from the primary tumor to its drainage sentinel lymph nodes (SLNs), we further demonstrate that this strategy would be helpful to the treatment of metastatic lymph nodes by nanoparticle-based PDT. Lastly, both enhanced EPR effect of NM-Ce6 and relieved hypoxia state of tumor are also observed after systemic injection of modified HAase, proving its potential for clinical translation. Therefore, our work presents a new concept to improve the efficacy of nanomedicine by modulating the tumor microenvironment. PMID:27022664

  6. Phthalocyanine-assisted photodynamic inactivation of pathogenic microorganisms

    NASA Astrophysics Data System (ADS)

    Mantareva, Vanya; Angelov, Ivan; Borissova, Ekaterina; Avramov, Latchezar; Kussovski, Vesselin

    2007-03-01

    The phthalocyanine zinc(II) and aluminum (III) complexes were studied to photoinactivate the bacterial strains, Staphylococcus aureus, methacillin-sensitive and methacillin-resistant, Pseudomonas aeruginosa and one yeast Candida albicans. The binding of phthalocyanines to bacteria and fungi cells was evaluated by the means of laserinduced fluorescence technique. The fluorescent spectra of dyes (650 - 800 nm) after direct excitation (635 nm) were measured as follows: 1. for the aqua supernatants obtained after 10 min cell incubation with the respected phthalocyanines (1.6 μmol.l -1), 2. for the washed from the unbound dye cells, and 3. for the organic extracts from the three times washed cells. Fluorescent intensities at the emission maximum (~690 nm) were compared to the spectra of the phthalocyanines in organic solutions. The phthalocyanines uptake data for bacteria and fungi were determined at different cell densities. Nevertheless the better fluorescence properties of AlPc (fluorescent quantum yield of 0.4 towards 0.3 for ZnPcs) the lower drug accumulation in microorganisms was obtained. PDI results indicated an intensive lowering of the bacterial survival of both strains of S. aureus treated with cationic ZnPcMe followed by the anionic ZnPcS, at irradiance of 100 mW cm -2 and fluence rate of 60 J cm -2. More resistant to phototreatment P. aeruginosa and morphologically complicated yeast C. albicans were successfully inactivated only with cationic ZnPcMe. These data indicate the promising future application of cationic phthalocyanine in photodynamic inactivation of pathogenic microorganisms.

  7. Effects of photodynamic therapy on the endocytic pathway

    PubMed Central

    Kessel, David; Price, Michael; Caruso, Joseph; Reiners, John

    2011-01-01

    In this report, we describe an effect of photodynamic therapy (PDT) on membrane trafficking in murine 1c1c7 hepatoma cells. A brief exposure of 1c1c7 cells to a 20 nM concentration of the phosphatidylinositol kinase class-3 antagonist wortmannin led to the rapid appearance of cytoplasmic vacuoles. Fluorescence monitoring of plasma membrane-associated 1-[4-(trimethylamino)-phenyl]-6-phenylhexa-1,3,5-triene (TDPH) over time demonstrated that the wortmannin-induced vacuoles were derived from endocytosed plasma membrane. Low-dose photodamage catalyzed by the lysosomal photosensitizer NPe6, prior to the addition of wortmannin, prevented formation of these vacuoles. NPe6 was found to suppress for several hours the normal trafficking of TDPH-labeled plasma membrane to the cytosol, and the formation of punctate TDPH-labeled cytoplasmic vesicles. The ability of NPe6-induced photodamage to suppress wortmannin-induced vacuolization occurred under conditions that did not disrupt lysosomes and were at or below the threshold of cytostatic/cytotoxic effects. Furthermore, the suppressive effects of NPe6-PDT were not prevented by inclusion of an agent that stabilized lysosomal membranes, or by E64d, an inhibitor of lysosomal cathepsin proteases. Mitochondrial photodamage was less effective at preventing wortmannin-induced vacuole formation and PDT directed against the ER had no effect. The role of photodamage to the endocytic pathway may be a hitherto unexplored effect on cells that selectively accumulate photosensitizing agents. These results indicate that photodamage directed against endosomes/lysosomes has effects independent of the release of lysosomal proteases. PMID:21125114

  8. Assessing autophagy in the context of photodynamic therapy

    PubMed Central

    Reiners, John J.; Agostinis, Patrizia; Berg, Kristian; Oleinick, Nancy L.; Kessel, David

    2010-01-01

    Photodynamic therapy (PDT) is a procedure that has applications in the selective eradication of neoplasia where sites of malignant lesions are clearly delineated. It is a two-step process whereby cells are first sensitized to light and then photoirradiated. This results in the formation of singlet molecular oxygen and other reactive oxygen species that can cause photodamage at sites where the photosensitizing agent has localized. Photosensitizers found to be clinically useful show affinity for the endoplasmic reticulum (ER), mitochondria, lysosomes, or combinations of these sites. The induction of apoptosis and/or autophagy in photosensitized cells is a common outcome of PDT. This report explores the following issues: (1) Does the induction of autophagy in PDT protocols occur independent of, or in association with, apoptosis? (2) Does the resulting autophagy play a prosurvival or prodeath role? (3) Do photosensitizers damage/inactivate specific proteins that are components of, or that modulate the autophagic process? (4) Can an autophagic response be mounted in cells in which lysosomes are specifically photodamaged? In brief, autophagy can occur independently of apoptosis in PDT protocols, and appears to play a prosurvival role in apoptosis competent cells, and a prodeath role in apoptosis incompetent cells. Mitochondrial and ER-localized sensitizers cause selective photodamage to some (i.e., Bcl-2, Bcl-xL, mTOR) proteins involved in the apoptotic/autophagic process. Finally, an aborted autophagic response occurs in cells with photodamaged lysosomes. Whereas autophagosomes form, digestion of their cargo is compromised because of the absence of functional lysosomes. PMID:19855190

  9. Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy.

    PubMed

    Kuzyniak, Weronika; Ermilov, Eugeny A; Atilla, Devrim; Gürek, Ayşe Gül; Nitzsche, Bianca; Derkow, Katja; Hoffmann, Björn; Steinemann, Gustav; Ahsen, Vefa; Höpfner, Michael

    2016-03-01

    Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 μM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT. PMID:26162500

  10. 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

  11. Theoretical spectroscopy and photodynamics of a ruthenium nitrosyl complex.

    PubMed

    Freitag, Leon; González, Leticia

    2014-07-01

    Photoactive transition-metal nitrosyl complexes are particularly interesting as potential drugs that deliver nitric oxide (NO) upon UV-light irradiation to be used, e.g., in photodynamic therapy. It is well-recognized that quantum-chemical calculations can guide the rational design and synthesis of molecules with specific functions. In this contribution, it is shown how electronic structure calculations and dynamical simulations can provide a unique insight into the photodissociation mechanism of NO. Exemplarily, [Ru(PaPy3)(NO)](2+) is investigated in detail, as a prototype of a particularly promising class of photoactive metal nitrosyl complexes. The ability of time-dependent density functional theory (TD-DFT) to obtain reliable excited-state energies compared with more sophisticated multiconfigurational spin-corrected calculations is evaluated. Moreover, a TD-DFT-based trajectory surface-hopping molecular dynamics study is employed to reveal the details of the radiationless decay of the molecule via internal conversion and intersystem crossing. Calculations show that the ground state of [Ru(PaPy3)(NO)](2+) includes a significant admixture of the Ru(III)(NO)(0) electronic configuration, in contrast to the previously postulated Ru(II)(NO)(+) structure of similar metal nitrosyls. Moreover, the lowest singlet and triplet excited states populate the antibonding metal d → πNO* orbitals, favoring NO dissociation. Molecular dynamics show that intersystem crossing is ultrafast (<10 fs) and dissociation is initiated in less than 50 fs. The competing relaxation to the lowest S1 singlet state takes place in less than 100 fs and thus competes with NO dissociation, which mostly takes place in the higher-lying excited triplet states. All of these processes are accompanied by bending of the NO ligand, which is not confined to any particular state. PMID:24745977

  12. 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.

  13. The design of a robotic multichannel platform for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hu, Yida; Finlay, Jarod C.; Zhu, Timothy C.

    2009-06-01

    A compact robotic platform is designed for simultaneous multichannel motion control for light delivery and dosimetry during interstitial photodynamic therapy (PDT). Movements of light sources and isotropic detectors are controlled by individual motors along different catheters for interstitial PDT. The robotic multichannel platform adds feedback control of positioning for up to 16 channels compared to the existing dual-motor system, which did not have positioning encoders. A 16-channel servo motion controller and micro DC motors, each with high resolution optical encoder, are adopted to control the motions of up to 16 channels independently. Each channel has a resolution of 0.1mm and a speed of 5cm/s. The robotic platform can perform light delivery and dosimetry independently, allowing arbitrary positioning of light sources and detectors in each catheter. Up to 16 compact translational channels can be combined according to different operational scheme with real-time optimal motion planning. The characteristic of high speed and coordinating motion will make it possible to use short linear sources (e.g., 1- cm) to deliver uniform PDT treatment to a bulk tumor within reasonable time by source stepping optimization of multiple sources simultaneously. Advanced robotic control algorithm handles the various unexpected circumstance in clinical procedure, e.g., positiontorque/ current control will be applied to prevent excessive force in the case of resistance in the fiber or motorized mechanism. The robotic platform is fully compatible with operation room (OR) environment and improves the light delivery and dosimetry in PDT. It can be adopted for diffusing optical tomography (DOT), spectroscopic DOT and fluorescent spectroscopy.

  14. Target cell specific antibody-based photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rosenblum, Lauren T.; Mitsunaga, Makoto; Kakareka, John W.; Morgan, Nicole Y.; Pohida, Thomas J.; Choyke, Peter L.; Kobayashi, Hisataka

    2011-03-01

    In photodynamic therapy (PDT), localized monochromatic light is used to activate targeted photosensitizers (PS) to induce cellular damage through the generation of cytotoxic species such as singlet oxygen. While first-generation PS passively targeted malignancies, a variety of targeting mechanisms have since been studied, including specifically activatable agents. Antibody internalization has previously been employed as a fluorescence activation system and could potentially enable similar activation of PS. TAMRA, Rhodamine-B and Rhodamine-6G were conjugated to trastuzumab (brand name Herceptin), a humanized monoclonal antibody with specificity for the human epidermal growth factor receptor 2 (HER2), to create quenched PS (Tra-TAM, Tra-RhoB, and Tra-Rho6G). Specific PDT with Tra-TAM and Tra-Rho6G, which formed covalently bound H-dimers, was demonstrated in HER2+ cells: Minimal cell death (<6%) was observed in all treatments of the HER2- cell line (BALB/3T3) and in treatments the HER2+ cell line (3T3/HER2) with light or trastuzumab only. There was significant light-induced cell death in HER2 expressing cells using Tra-TAM (3% dead without light, 20% at 50 J/cm2, 46% at 100 J/cm2) and Tra-Rho6G (5% dead without light, 22% at 50 J/cm2, 46% at 100 J/cm2). No efficacy was observed in treatment with Tra-RhoB, which was also non-specifically taken up by BALB/3T3 cells and which had weaker PS-antibody interactions (as demonstrated by visualization of protein and fluorescence on SDS-PAGE).

  15. In vitro experimental photodynamic diagnosis of artery atherosclerosis

    NASA Astrophysics Data System (ADS)

    Bialy, Dariusz; Derkacz, Arkadiusz; Wawrzynska, M.; Kwasny, Miroslaw; Strek, Wieslaw; Protasiewicz, Marcin

    2004-07-01

    Background: Although there are several methods for atherosclerosis detection available, none of them seems to be accurate enough to identify the vulnerable atheroscleroitc plaque. Photodynamic diagnosis (PDD) and therapy (PDT) -- a new method evaluated for neoplasms treatment is a modern approach to detecting and treating atherosclerosis. Aim: The purpose of this study was to assess in vitro the capability of PDD with use of chlorin e6 to recognize atherosclerotic plaque and its usefulness as a feedback system for photoangioplasty treatment. Methods: 30 specimens of human aorta. The samples were soaked with chlorin e6 and then washed out. The luminescence spectra were then collected. All samples were examined with light microscopy. Results: Tissue fluorescence is seen as green light. We noted a very strong red fluorescence of chlorin e6 originating from lipid reach plaque. We established a quantitative factor which would be the ratio R of chlorin e6 red intensity in its 660 nm maximum compared to the area of green luminescence centered at 515 nm. The highest value of the ratio was reached at atheromatous samples, then calcified and normal ones R2 = 3.51 +/- 0.62, R3 = 1.63 +/- 0.31, R1 = 1.51 +/- 0.15 respectively. Statistically significant difference was noted between group two and one and between group two and three R2 = 3.51 +/- 0.62 vs R3 = 1.63 +/- 0.31 (p < 0,05); R2 = 3.51 +/- 0.62 vs. R1 = 1.51 +/- 0.15 (p<0.05) respectively. Conclusions: the following in vitro study confirms that photosensitizer chlorin e6 accumulates within atheromatous plaque. It may be a specific tool for atheromatous and normal or calcified segments discrimination. The advantage of the above method is a possibility of a real time imaging followed by targeted therapy of various forms and stages of atherosclerosis.

  16. Novel nanostructural photosensitizers for photodynamic therapy: in vitro studies.

    PubMed

    Nawalany, Kinga; Rusin, Aleksandra; Kepczynski, Mariusz; Filipczak, Piotr; Kumorek, Marta; Kozik, Bartłomiej; Weitman, Hana; Ehrenberg, Benjamin; Krawczyk, Zdzisław; Nowakowska, Maria

    2012-07-01

    Photosensitizing properties of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP) functionalized by covalent attachment of one chain of poly(ethylene glycol) (PEG) with a molecular weight of 350, 2000, or 5000 Da (p-THPP-PEG(350), p-THPP-PEG(2000), p-THPP-PEG(5000)) were studied in vitro. Dark and photo cytotoxicity of these photosensitizers delivered in solution or embedded in liposomes were evaluated on two cell lines: a human colorectal carcinoma cell line (HCT 116) and a prostate cancer cell line (DU 145), and compared with these treated with free p-THPP. The attachment of PEG chains results in the pronounced reduction of the dark cytotoxicity of the parent porphyrin. Cell viability tests have demonstrated that the phototoxicity of pegylated porphyrins is dependent on the length of PEG chain and p-THPP-PEG(2000) exhibited the highest photodynamic efficacy for both cell lines. The encapsulation into liposomes did not improve the PDT effect. However, the liposomal formulation of p-THPP-PEG(2000) showed a greater tendency to induce apoptosis in both cell lines than the parent or pegylated porphyrin delivered in solution. The colocalization of p-THPP, p-THPP-PEG(2000) and p-THPP-PEG(2000) enclosed in liposomes with fluorescent markers for lysosomes, mitochondria, endoplasmatic reticulum (ER) and Golgi apparatus (GA) was determined in the HCT 116 line. The p-THPP exhibited ubiquitous intracellular distribution with a preference for membranes: mitochondria, ER, GA, lysosomes and plasma membrane. Fluorescence of p-THPP-PEG(2000) was observed within the cytoplasm, with a stronger signal detected in membranous organelle: mitochondria, ER, GA and lysosomes. In contrast, p-THPP-PEG(2000) delivered in liposomes gave a distinct lysosomal pattern of localization. PMID:22525077

  17. Photodynamic decontamination of foodstuff from Staphylococcus aureus based on novel formulations of curcumin.

    PubMed

    Tortik, Nicole; Spaeth, Andreas; Plaetzer, Kristjan

    2014-10-01

    Increasing antibiotic resistance is one of the world's greatest health problems. The food chain is an important factor in the transfer of resistant germs from animals to humans. This study focuses on photodynamic inactivation (PDI), employing curcumin bound to polyvinylpyrrolidone (PVP-C) and NovaSol®-curcumin as photosensitizers, as potent tool for the decontamination of cucumber, pepper and chicken meat from Staphylococcus aureus (serving as the model for methicillin-resistant S. aureus, MRSA). Both curcumin and PVP have been approved as food additives, consequently exhibiting excellent biocompatibility. Vegetables and meat were contaminated with S. aureus and sprinkled with PVP-C and NovaSol®-curcumin at concentrations of 50 and 100 μM, respectively. Illumination was performed immediately using visible light (435 nm, 9.4 mW cm(-2), 33.8 J cm(-2)). The PDI efficiency was determined by quantitative analyses of colony forming units 24 h post illumination. Additionally, the long-term effects of the photodynamic inactivation on cucumbers were investigated by quantitative analyses of the viable bacterial fraction after 24 and 48 h. Photodynamic inactivation of S. aureus revealed a mean reduction of 2.6 log10 (99.8%) for cucumbers, 2.5 log10 (99.7%) for pepper and 1.7 log10 (98%) for chicken meat relative to control samples. The bactericidal effect compared to controls seems to last for at least 48 h. Furthermore, no visible changes of the exterior appearance of foodstuff after photodynamic decontamination were observed. Photodynamic inactivation may therefore constitute a safe, economic and effective decontamination technique, which is harmless to health and not noticeable to consumers. PMID:24957403

  18. 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-γ) photodynamic therapy potentially offers much higher treatment selectivity than its one-photon (1-γ) counterpart. By utilizing focused light for 2-γ 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-γ 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-γ photodynamic therapy we measured 2-γ 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-γ 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-γ PDT with verteporfin in vivo. Although we were able to induce photodynamic damage to a blood vessel using 1-γ excitation, 2-γ excitation resulted in no visible damage to irradiated blood vessel. The most probable reason is low efficiency of verteporfin as a 2-γ photosensitizer. We also report 2-γ spectrum of new photosensitizer, HCC4 (4300 GM at 830 nm), specifically designed for efficient 2-γ excitation.

  19. 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

  20. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

    NASA Astrophysics Data System (ADS)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-06-01

    Correction for `Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a.

  1. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy.

    PubMed

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-07-01

    Correction for 'Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a. PMID:27300478

  2. Design and Measurement of a 1-kBit eFuse One-Time Programmable Memory IP Based on a BCD Process

    NASA Astrophysics Data System (ADS)

    Kim, Du-Hwi; Jang, Ji-Hye; Jin, Liyan; Lee, Jae-Hyung; Ha, Pan-Bong; Kim, Young-Hee

    We propose a low-power eFuse one-time programmable (OTP) memory IP based on a bipolar CMOS DMOS (BCD) process. It is an eFuse OTP memory cell which uses separate transistors that are optimized in program and in read mode. The eFuse cell also uses poly-silicon gates having co-silicide. An asynchronous interface and a separate I/O method are used for the low-power and small-area eFuse OTP memory IP. Additionally, we propose a new circuit protecting a short-circuit current in the VDD-to-VIO voltage level translator circuit while the VDD voltage is being generated by the voltage regulator at power-up. A digital sensing circuit using clocked inverters is used to sense a bit-line (BL) datum. Furthermore, the poly-silicon of the IP is split into n+ poly-silicon and p+ poly-silicon to optimize the eFuse link. The layout size of the designed eFuse OTP memory IP with Dongbu HiTek's 0.18µm BCD process is 283.565 × 524.180µm2. It is measured by manufactured test IPs with Dongbu HiTek's 0.18µm BCD process that the programming voltage of the n+ gate poly-silicon is about 0.1V less than that of the p+ gate poly-silicon.

  3. Cryptanalysis of Controlled Quantum Secure Direct Communication and Authentication Protocol Based on Five-Particle Cluster State and Quantum One-Time Pad

    NASA Astrophysics Data System (ADS)

    Liu, Zhihao; Chen, Hanwu; Liu, Wenjie

    2016-06-01

    A new attack strategy, the so-called intercept-selectively-measure-resend attack is put forward. It shows that there are some security issues in the controlled quantum secure direct communication (CQSDC) and authentication protocol based on five-particle cluster states and quantum one-time pad. Firstly, an eavesdropper (Eve) can use this attack to eavesdrop on 0.656 bit of every bit of the identity string of the receiver and 1.406 bits of every couple of the corresponding bits of the secret message without being detected. Also, she can eavesdrop on 0.311 bit of every bit of the identity string of the controller. Secondly, the receiver can also take this attack to obtain 1.311 bits of every couple of the corresponding bits of the secret message without the permission of the controller, which is not allowed in the CQSDC protocols. In fact, there is another security issue in this protocol, that is, one half of the information about the secret is leaked out unconsciously. In addition, an alternative attack strategy which is called as the selective-CNOT-operation attack strategy to attack this protocol is discussed.

  4. Comparison of membrane-protective activity of antioxidants quercetine and Gratiola Officinalis L. extract under conditions of photodynamic haemolysis

    NASA Astrophysics Data System (ADS)

    Tkachenko, N. V.; Bykova, E. V.; Pravdin, A. B.; Navolokin, N. A.; Polukonova, N. V.; Bucharskaya, A. B.; Mudrak, D. A.; Prilepskii, A. Y.

    2016-04-01

    In the present work the effectiveness of antioxidants quercetine (a pure chemical) and Gratiola officinalis extract, which is obtained by a new method of extraction from plant material, is investigated on the model of photodynamic haemolysis that is a rather convenient method to monitor the rate of cell membranes oxidative destruction. The effect of these antioxidants on the rate of photodynamic haemolysis is considered as a measure of membranoprotective efficiency.

  5. Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line.

    PubMed Central

    Datta, S. N.; Allman, R.; Loh, C.; Mason, M.; Matthews, P. N.

    1997-01-01

    Photodynamic therapy is a method for treating cancer using drugs activated by light. A new compound, 5-aminolaevulinic acid (ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. Cell survival of ALA-mediated photodynamic therapy was measured in the J82 bladder cancer cell line, along with its mitomycin C-resistant counterpart J82/MMC. This demonstrated that mitomycin resistance is not cross-resistant to photodynamic therapy. There was also a suggestion that the mitomycin-resistant cells were more susceptible to photodynamic therapy than the parent cell line. Photodynamic therapy appeared to enhance the effect of mitomycin C, when mitomycin C was given first. This phenomenon was apparent for both drug-resistant and drug-sensitive cell lines. This suggests a possible role for combined mitomycin C and photodynamic therapy in superficial bladder tumours that have recurred despite intravesical cytotoxic drug treatment. PMID:9252197

  6. Comparative survival study of glial cells and cells composing walls of blood vessels in crustacean ventral nerve cord after photodynamic treatment

    NASA Astrophysics Data System (ADS)

    Kolosov, Mikhail S.; Shubina, Elena

    2015-03-01

    Photodynamic therapy is a prospective treatment modality of brain cancers. It is of importance to have information about relative survival rate of different cell types in nerve tissue during photodynamic treatment. Particularly, for development of sparing strategy of the photodynamic therapy of brain tumors, which pursuits both total elimination of malignant cells, which are usually of glial origin, and, at the same time, preservation of normal blood circulation as well as normal glial cells in the brain. The aim of this work was to carry out comparative survival study of glial cells and cells composing walls of blood vessels after photodynamic treatment, using simple model object - ventral nerve cord of crustacean.

  7. Photodynamic actinometry using microencapsulates: concepts and developmental approach

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Austin, James; Wilson, Brian C.; Lilge, Lothar D.

    2003-12-01

    This study describes the development of novel, fluorescent-based actinometer encapsulates as a means of discerning volumetric Photodynamic therapy (PDT) dosimetry relative to the incident light and reactive oxygen species (ROS) production. PDT relies on three main ingredients; oxygen, light and photo-activatable commpounds, although, the PDT response is definately contingent on the site and level of ROS generation. Providing a localized, in situ measurement of luminance and ROS generation is therefore critical when deciphering targetd photodynamci therapy (PDT) protocols in vivo. Toward this end, alginate-poly-L-lysine-alginate encapsulates were made using ionotropic gelation of sodium alginate droplets ranging from 75 to 200 μm in diameter. Two candidate dyes, ADS680WS (ADS) and R-phycoerythrin (RPE) were chosen based on photochemistry, chemical stabilty and sensitivity to changing pH and oxygen environments. Alginate beads were constructed with ADS conjugated to the inside and RPE attached to the outside layer. The production of ROS was initiated either chemically using increasing concentrations of potassium perchromate or photochemically using tetra-sulphonated aluminium phosphorescence (AlPcS4). The generation of singlet oxygen was confirmed by the presence of a phosphorescence peak at 1270 nm. The resulting photodegradation and subsequent decrease in fluorescence of RPE was found to correlate very closely (p<0.001) with increasing perchromate or fluence respectively. This effect was independent of pH (6.5-8) and could be inhibited using sodium azide. RPA was not susceptible to photobleaching with light alone (675 nm; 150 J/cm2). Meanwhile, ADS680WS, which absorbs light at 670-690 nm, showed a direct correlation between diminished fluorescence (photobleaching) and incident fluence (675 nm; 0-100 J/cm2). This effect was independent of fluence rate (10-40 mW/cm2). We propose that actinometer encapsulates may prove useful for implanting into potential target

  8. 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

  9. 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-1α was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized

  10. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Khaing Oo, Maung Kyaw

    As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered surface charges by photo-reduction of gold chloride salt using branched polyethyleneimine and sodium citrate respectively. An optimal concentration window of gold salt has been established to yield the most stable and monodispersed gold nanoparticles. 5-aminolevulinic acid (5-ALA), a photosensitizing precursor, has been successfully conjugated on to positively charged gold nanoparticles through electrostatic interactions. The 5-ALA/gold nanoparticle conjugates are biocompatible and have shown to be preferably taken up by cancer cells. Subsequent light irradiation results in the generation of reactive oxygen species (ROS) in cancer cells, leading to their destruction without adverse effects on normal fibroblasts. We have demonstrated for the first time that gold nanoparticles can enhance PDT efficacy by 50% compared to the treatment with 5-ALA alone. Collected evidence has strongly suggested that this enhancement stems from the elevated formation of ROS via the strongly localized electric field of gold nanoparticles. Through single cell imaging using surface-enhanced Raman scattering enabled by the very same gold nanoparticles, we have shown that multifunctionality of gold nanoparticles can be harvested concurrently for biomedical applications in general and for PDT in specific. In other words, gold nanoparticles can be used not only for targeted drug delivery and field-enhanced ROS formation, but also for monitoring cell destructions during PDT. Finally, our COMSOL Multiphysics simulation of the size-dependent electric

  11. Effects of photodynamic therapy on adhesion molecules and metastasis.

    PubMed

    Rousset, N; Vonarx, V; Eléouet, S; Carré, J; Kerninon, E; Lajat, Y; Patrice, T

    1999-01-01

    Photodynamic therapy (PDT) induces among numerous cell targets membrane damage and alteration in cancer cell adhesiveness, an important parameter in cancer metastasis. We have previously shown that hematoporphyrin derivative (HPD)-PDT decreases cancer cell adhesiveness to endothelial cells in vitro and that it reduces the metastatic potential of cells injected into rats. The present study analyzes the influence of PDT in vivo on the metastatic potential of cancers cells and in vitro on the expression of molecules involved in adhesion and in the metastatic process. Photofrin and benzoporphyrin derivative monoacid ring A (BPD) have been evaluated on two colon cancer cell lines obtained from the same cancer [progressive (PROb) and regressive (REGb)] with different metastatic properties. Studies of BPD and Photofrin toxicity and phototoxicity are performed by colorimetric MTT assay on PROb and REGb cells to determine the PDT doses inducing around 25% cell death. Flow cytometry is then used to determine adhesion-molecule expression at the cell surface. ICAM-I, MHC-I, CD44V6 and its lectins (àHt1.3, PNA, SNA and UEA) are studied using cells treated either with BPD (50 ng/ml, 457 nm light, 10 J/cm2) or Photofrin (0.5 microgram/ml, 514 nm light, 25 J/cm2). Changes of metastatic patterns of PROb cells have been assessed by the subcutaneous injection of non-lethally treated BPD or Photofrin cells and counting lung metastases. First, we confirm the metastatic potential reduction induced by PDT with respectively a 71 or 96% decrease of the mean number of metastases (as compared with controls) for PROb cells treated with 50 ng/ml BPD and 10 or 20 J/cm2 irradiation. Concerning Photofrin-PDT-treated cells, we find respectively a 90 or 97% decrease (as compared with controls) of the mean number of metastases for PROb cells treated with 0.5 microgram/ml Photofrin and 25 or 50 J/cm2 irradiation. Then, we observe that CD44V6, its lectins (àHt1.3, PNA, SNA) and MHC-I are

  12. Half-dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

    PubMed Central

    Naseripour, Masood; Falavarjani, Khalil Ghasemi; Sedaghat, Ahad; Moghaddam, Arezoo Karimi; Nasserisina, Sadaf; Alemzadeh, Sayyed Amirpooya

    2016-01-01

    Purpose: To report the outcomes of half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). Methods: A chart review of patients with chronic CSC who had received half-dose verteporfin PDT (3 mg/m2) was performed. The main outcome measures were resolution of subretinal fluid and best corrected visual acuity (BCVA). Results: Fifty-three eyes of 51 patients with mean age of 45.01 ± 8.9 years were studied. Three, 6 and 12 months after half-dose PDT, subretinal fluid was completely resolved in 51 eyes (96.2%). In 2 eyes (one patient), subretinal fluid decreased at 3 months but one year later, an increase in subretinal fluid was detected on optical coherence tomography (OCT) which completely resolved following additional PDT. Another patient with recurrence of subretinal fluid rejected further treatment. Mean baseline central subfield thickness was 385 ± 113.0 μm which was decreased to 235 ± 39.7, 247 ± 49.7, and 244 ± 49.52 μm after 3, 6 and 12 months, respectively (all P-values < 0.001). Mean BCVA was 0.33 ± 0.27 LogMAR before PDT and 0.11 ± 0.18, 0.11 ± 0.17, 0.17 ± 0.26 and 0.10 ± 0.23 LogMAR, 3, 6 and 12 months and at final visit (up to 60 months) after PDT, respectively (all P-values < 0.001). Improvement ≥2 lines in BCVA occurred in 20 eyes (37.7%). Statistically significant correlations were found between improvement in BCVA and baseline BCVA, baseline central subfield thickness and central subfield thickness after resorption of subretinal fluid (P < 0.001, P= 0.04 and P= 0.01, respectively). No complications attributed to PDT were observed. Conclusion: Half-dose PDT is effective for treatment of patients with chronic CSC. PMID:27195088

  13. Optimization of light dosimetry for photodynamic therapy of Barrett's esophagus

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Phan, Mary N.; Overholt, Bergein F.; Haydek, John M.

    2004-06-01

    Background and Objective: Photodynamic therapy (PDT) may be used for ablation of high grade dysplasia and/or early cancer (HGD/T1) in Barrett's esophagus. A complication of PDT is esophageal stricture. The objective of this study was to find the lowest light dose to potentially reduce the incidence of strictures while effectively ablating HGD/T1. Materials and Methods: Patients (n=113) with HGD/T1 received an intravenous injection of porfimer sodium (2 mg/kg). Three days later, laser light (630 nm) was delivered using a cylindrical diffuser inserted in a 20 mm.diameter PDT balloon. Patients were treated at light doses of 115 J/cm, 105 J/cm, 95 J/cm and 85 J/cm. The efficacy was determined by four quadrant biopsies of the treated area three months after PDT. The formation of stricture was determined by the incidence of dysphagia and the need for esophageal dilation. Strictures were considered mild if they required less than 6 dilations, and severe if 6 or more dilations were required. Efficacy and incidence of strictures were tabulated as a function of light dose. Results: Using 115 J/cm, there were 17% of patients with residual HGD/T1 after one treatment. However, when the light doses of 105 J/cm, 95 J/cm and 85 J/cm were used, the residual HGD/T1 after one PDT session was increased to 33%, 30%, and 32% respectively. The overall incidence of strictures (mild and severe) was not correlated to the light dose. However, the incidence of severe strictures was directly proportional to the light dose. Using the light dose of 115 J/cm, 15.3% of patients developed severe strictures compared to about 5% in the groups of patients who received the lower light doses. Conclusions: Decreasing the light dose below 115 J/cm doubled the rate of residual HGD/T1 after one treatment while reducing the incidence of severe strictures to one-third of cases from 115 J/cm. The results may be used to evaluate the risks and benefits of different light doses.

  14. In vivo photodynamic inactivation of Psuedomonas aeruginosa in burned skin in rats

    NASA Astrophysics Data System (ADS)

    Hirao, Akihiro; Sato, Shunichi; Terakawa, Mitsuhiro; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Obara, Minoru

    2010-02-01

    Control of infection in wounds is critically important to avoid transition to sepsis; however, recent rise of drug-resistant bacteria makes it difficult. Thus, antimicrobial photodynamic therapy (APDT) has recently received considerable attention. In this study, we examined methylene blue (MB)-mediated photodynamic inactivation of Psuedomonas aeruginosa in rat burned skin. Two days after infection, the wound surface was contacted with a MB solution at different concentrations, and thereafter the wound was irradiated with cw 665-nm light at a constant power density of 250 mW/cm2 for different time durations. We obtained a two orders of magnitude decrease in the number of bacteria by PDT with a 2-h contact of 0.5-mM MB solution and a illumination of 480 J/cm2, demonstrating the efficacy of PDT against infection with Ps. aeruginosa in burns.

  15. Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

    Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

  16. Hematoporphyrin-derivative photodynamic in-vitro sensitivity testing for brain tumors

    NASA Astrophysics Data System (ADS)

    Plattner, Michael; Bernwick, Walter; Kostron, Herwig

    1993-03-01

    Brain tumors of various histologies were subjected to an in-vitro photodynamic-sensitivity test. The studies were performed on primary cultures of human glioblastomas, meningiomas, and ependymomas, which were exposed to increasing concentrations of hematoporphyrin derivative and 60 J/cm2 delivered by an argon-dye laser at 632 nm. A growth inhibition of 75% was demonstrated at a concentration of 25 (mu) g and 10 (mu) g HPD/ml medium for two different glioblastomas, respectively. A growth inhibition of 75% was observed in the ependymoma line at 10 and 50 (mu) g HPD/ml with and without light, respectively. The meningioma demonstrated a 75% inhibition already at (mu) g and 75 (mu) g/ml medium with and without light, respectively. These results demonstrate a significant difference in the response of brain tumors to photodynamic treatment (PDT). In vitro-PDT-assay should be taken into account if clinical application of PDT is considered.

  17. Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy.

    PubMed

    Babii, Oleg; Afonin, Sergii; Garmanchuk, Liudmyla V; Nikulina, Viktoria V; Nikolaienko, Tetiana V; Storozhuk, Olha V; Shelest, Dmytro V; Dasyukevich, Olga I; Ostapchenko, Liudmyla I; Iurchenko, Volodymyr; Zozulya, Sergey; Ulrich, Anne S; Komarov, Igor V

    2016-04-25

    Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene-derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light-sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV-generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light. PMID:27028784

  18. Clinical effect of photodynamic therapy on primary carious dentin after partial caries removal.

    PubMed

    Neves, Pierre Adriano Moreno; Lima, Leonardo Abrantes; Rodrigues, Fernanda Cristina Nogueira; Leitão, Tarcisio Jorge; Ribeiro, Cecília Cláudia Costa

    2016-05-20

    This study was conducted to assess the clinical effect of photodynamic therapy (PDT) in the decontamination of the deep dentin of deciduous molars submitted to partial removal of carious tissue. After cavity preparation, dentin samples were taken from the pulp wall of nineteen deciduous molars before and after PDT application. Remaining dentin was treated with 0.01% methylene blue dye followed by irradiation with an InGaAlP diode laser (λ - 660 nm; 40 mW; 120 J/cm2; 120 s). Dentin samples were microbiologically assessed for the enumeration of total microorganisms, Lactobacillus spp. and mutans streptococci. There was no significant difference in the number of colony-forming units (CFU) for any of the microorganisms assessed (p > 0.05). Photodynamic therapy, using 0.01% methylene blue dye at a dosimetry of 120 J/cm2 would not be a viable clinical alternative to reduce bacterial contamination in deep dentin. PMID:27223131

  19. Pharmaceutical development, composition and quantitative analysis of phthalocyanine as the photosensitizer for cancer photodynamic therapy.

    PubMed

    Jiang, Zhou; Shao, Jingwei; Yang, Tingting; Wang, Jian; Jia, Lee

    2014-01-01

    Phthalocyanine (Pc) and its related derivatives are a class of functional materials that are easily activated by the light at a special wavelength. As such photosensitizer, Pc has been applied to photodynamic therapy (PDT), in addition to its broad applications in many fields, for both malignant and benign diseases. One of our long-term research focuses is to develop Pc for cancer therapy. Herein we briefly review mechanisms of action of Pc used for photodynamic therapy, its pharmaceutical development and molecular modification to enhance its drugability and improve its intracellular localization. We also describe the current status of the Pc derivatives under clinical investigation, and analyze the methods used for quantitative analysis of those Pc derivatives. PMID:23746989

  20. Investigation of Water-Soluble X-ray Luminescence Nanoparticles for Photodynamic Activation

    SciTech Connect

    Liu, Yuanfang; Chen, Wei; Wang, Shaopeng; Joly, Alan G.

    2008-01-28

    In this letter, we report the synthesis of LaF3:Tb3+-MTCP (meso-Tetra(4-carboxyphenyl) porphine) nanoparticle conjugates and investigate the energy transfer as well as singlet oxygen generation following X-ray irradiation. Our observations indicate that LaF3:Tb3+-MTCP nanoparticle conjugates are efficient photodynamic agents that can be initiated by X-rays at a reasonably low dose. The addition of folic acid to facilitate targeting to folate receptors on tumor cells has no effect on the quantum yield of singlet oxygen in the nanoparticle-MTCP conjugates. Our pilot studies indicate that water-soluble scintillation nanoparticles can be potentially used to activate photodynamic therapy as a promising deep cancer treatment.