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Sample records for photodynamic therapy agents

  1. 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.

  2. 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

  3. 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.

  4. 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 ...

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Mfouo-Tynga, Ivan; Abrahamse, Heidi

    2015-01-01

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

  9. 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

  10. Near-infrared Au nanorods in photodynamic therapy, hyperthermia agents, and near-infrared optical imaging

    NASA Astrophysics Data System (ADS)

    Kuo, Wen-Shuo; Chang, Chich-Neng; Chang, Yi-Ting; Yang, Meng-Heng; Chien, Yi-Hsin; Chen, Shean-Jen; Yeh, Chen-Sheng

    2011-03-01

    The development of multifunctional nanomaterials is currently a topic of interest in the field of nanotechnology. Integrated systems that incorporate therapeutics, molecular targeting, and diagnostic imaging capabilities are considered to be the next generation of multifunctional nanomedicine. In this work, we present the first example of using Au nanorods simultaneously serving not only as photodynamic and photothermal agents to destroy A549 malignant cells but also as optical contrast agents simultaneously to monitor cellular image. Au nanorods were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and hyperthermia. With the combination of PDT and hyperthermia proved to be efficiently killing cancer cells as compared to PDT or hyperthermia treatment alone and enhanced the effectiveness of photodestruction. Moreover, Au nanorods conjugated with ICG displayed high chemical stability and simultaneously acted as a promising cellular image probe. As a result, the preparation of Au nanorods conjugated with photosensitizers as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  11. Efficacy of gallium phthalocyanine as a photosensitizing agent in photodynamic therapy for the treatment of cancer

    NASA Astrophysics Data System (ADS)

    Maduray, Kaminee; Odhav, Bharti

    2012-12-01

    Photodynamic therapy is a revolutionary treatment aimed at treating cancers without surgery or chemotherapy. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. porphyrins, phthalocyanines, etc.) can kill cancerous cells when exposed to low level laser light at a specific wavelength. The present study investigates the cellular uptake and photodynamic effect of gallium (III) phthalocyanine chloride (GaPcCl) on Caco-2 cancer cells. Caco-2 cells were treated with different concentrations of GaPcCl for 2 h before treatment with a diode laser (λ = 661 nm, laser power = 90 mW) delivering a light dose of 2.5 J/cm2, 4.5 J/cm2 or 8.5 J/cm2. After 24 h, the cell viability of post-irradiated cells was measured using the MTT assay. Cellular uptake studies were performed by photosensitizing cells with GaPcCl for 30 min, 2 h, 10 h, 12 h, 18 h and 24 h before lysing the treated cells into solution to measure the GaPcCl fluorescence emission at an excitation wavelength of 600 nm. Results showed an increase in fluorescence intensity of emission peaks at longer incubation times, indicating a greater cellular uptake of GaPcCl by Caco-2 cells at 24 h in comparison to 30 min. GaPcCl at a concentration of 100 μg/ml activated with a laser light dose of 8.5 J/cm2 reduced the cell viability of Caco-2 cells to 27%. This concludes that GaPcCl activated with low level laser light can be used as a photosensitizing agent for the in vitro PDT treatment of colon cancer.

  12. Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen.

    PubMed

    Wang, Xinning; Tsui, Brian; Ramamurthy, Gopolakrishnan; Zhang, Ping; Meyers, Joseph; Kenney, Malcolm E; Kiechle, Jonathan; Ponsky, Lee; Basilion, James P

    2016-08-01

    Prostatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1-PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1-PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834-44. ©2016 AACR. PMID:27297866

  13. In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

    SciTech Connect

    Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

    2009-01-01

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

  14. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    SciTech Connect

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  15. Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications.

    PubMed

    Nam, Jung Seung; Kang, Myeong-Gyun; Kang, Juhye; Park, Sun-Young; Lee, Shin Jung C; Kim, Hyun-Tak; Seo, Jeong Kon; Kwon, Oh-Hoon; Lim, Mi Hee; Rhee, Hyun-Woo; Kwon, Tae-Hyuk

    2016-08-31

    Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen ((1)O2) and superoxide radical (O2(•-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes. PMID:27494510

  16. Gold nanorods as dual photo-sensitizing and imaging agents for two-photon photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Tingting; Shen, Xiaoqin; Li, Lin; Guan, Zhenping; Gao, Nengyue; Yuan, Peiyan; Yao, Shao Q.; Xu, Qing-Hua; Xu, Guo Qin

    2012-11-01

    Gold nanorods with three different aspect ratios were prepared and their dual capabilities for two-photon imaging and two-photon photodynamic therapy have been demonstrated. These gold nanorods exhibit large two-photon absorption action cross-sections, about two orders of magnitude larger than small organic molecules, which makes them suitable for two-photon imaging. They can also effectively generate singlet oxygen under two-photon excitation, significantly higher than traditional photosensitizers such as Rose Bengal and Indocyanine Green. Such high singlet oxygen generation capability under two-photon excitation was ascribed to their large two-photon absorption cross-sections. Polyvinylpyrrolidone (PVP) coated gold nanorods displayed excellent biocompatibility and high cellular uptake efficiency. The two-photon photodynamic therapy effect and two-photon fluorescence imaging properties of PVP coated gold nanorods have been successfully demonstrated on HeLa cells in vitro using fluorescence microscopy and indirect XTT assay method. These gold nanorods thus hold great promise for imaging guided two-photon photodynamic therapy for the treatment of various malignant tumors.Gold nanorods with three different aspect ratios were prepared and their dual capabilities for two-photon imaging and two-photon photodynamic therapy have been demonstrated. These gold nanorods exhibit large two-photon absorption action cross-sections, about two orders of magnitude larger than small organic molecules, which makes them suitable for two-photon imaging. They can also effectively generate singlet oxygen under two-photon excitation, significantly higher than traditional photosensitizers such as Rose Bengal and Indocyanine Green. Such high singlet oxygen generation capability under two-photon excitation was ascribed to their large two-photon absorption cross-sections. Polyvinylpyrrolidone (PVP) coated gold nanorods displayed excellent biocompatibility and high cellular uptake efficiency

  17. In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

    PubMed Central

    Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

    2014-01-01

    In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

  18. 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.

  19. 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

  20. 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 ...

  1. 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

  2. Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).

    PubMed

    Kue, Chin Siang; Kamkaew, Anyanee; Lee, Hong Boon; Chung, Lip Yong; Kiew, Lik Voon; Burgess, Kevin

    2015-01-01

    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316

  3. ROS-Responsive Activatable Photosensitizing Agent for Imaging and Photodynamic Therapy of Activated Macrophages

    PubMed Central

    Kim, Hyunjin; Kim, Youngmi; Kim, In-Hoo; Kim, Kyungtae; Choi, Yongdoo

    2014-01-01

    The optical properties of macrophage-targeted theranostic nanoparticles (MacTNP) prepared from a Chlorin e6 (Ce6)-hyaluronic acid (HA) conjugate can be activated by reactive oxygen species (ROS) in macrophage cells. MacTNP are nonfluorescent and nonphototoxic in their native state. However, when treated with ROS, especially peroxynitrite, they become highly fluorescent and phototoxic. In vitro cell studies show that MacTNP emit near-infrared (NIR) fluorescence inside activated macrophages. The NIR fluorescence is quenched in the extracellular environment. MacTNP are nontoxic in macrophages up to a Ce6 concentration of 10 μM in the absence of light. However, MacTNP become phototoxic upon illumination in a light dose-dependent manner. In particular, significantly higher phototoxic effect is observed in the activated macrophage cells compared to human dermal fibroblasts and non-activated macrophages. The ROS-responsive MacTNP, with their high target-to-background ratio, may have a significant potential in selective NIR fluorescence imaging and in subsequent photodynamic therapy of atherosclerosis with minimum side effects. PMID:24396511

  4. Targeted PDT Agent Eradicates TrkC Expressing Tumors via Photodynamic Therapy (PDT)

    PubMed Central

    2015-01-01

    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for 1O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC– cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC–-photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC– tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC– tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316

  5. A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms.

    PubMed

    George, Blassan Plackal Adimuriyil; Abrahamse, Heidi

    2016-01-01

    This review article presents an extensive examination of risk factors for breast cancer, treatment strategies with special attention to photodynamic therapy and natural product based treatments. Breast cancer remains the most commonly occurring cancer in women worldwide and the detection, treatment, and prevention are prominent concerns in public health. Background information on current developments in treatment helps to update the approach towards risk assessment. Breast cancer risk is linked to many factors such as hereditary, reproductive and lifestyle factors. Minimally invasive Photodynamic therapy (PDT) can be used in the management of various cancers; it uses a light sensitive drug (a photosensitizer, PS) and a light of visible wavelength, to destroy targeted cancer cells. State of the art analyses has been carried out to investigate advancement in the search for the cure and control of cancer progression using natural products. Traditional medicinal plants have been used as lead compounds for drug discovery in modern medicine. Both PDT and plant derived drugs induce cell death via different mechanisms including apoptosis, necrosis, autophagy, cell cycle regulation and even the regulation of various cell signalling pathways. PMID:26499768

  6. Iron oxide nanoparticles functionalized with novel hydrophobic and hydrophilic porphyrins as potential agents for photodynamic therapy.

    PubMed

    Penon, Oriol; Marín, María J; Amabilino, David B; Russell, David A; Pérez-García, Lluïsa

    2016-01-15

    The preparation of novel porphyrin derivatives and their immobilization onto iron oxide nanoparticles to build up suitable nanotools for potential use in photodynamic therapy (PDT) has been explored. To achieve this purpose, a zinc porphyrin derivative, ZnPR-COOH, has been synthesized, characterized at the molecular level and immobilized onto previously synthesized iron oxide nanoparticles covered with oleylamine. The novel nanosystem (ZnPR-IONP) has been thoroughly characterized by a variety of techniques such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, X-ray photoloectron spectroscopy (XPS) and transmission electron microscopy (TEM). In order to probe the capability of the photosensitizer for PDT, the singlet oxygen production of both ZnPR-IONP and the free ligand ZnPR-COOH have been quantified by measuring the decay in absorption of the anthracene derivative 9,10-anthracenedipropionic acid (ADPA), showing an important increase on singlet oxygen production when the porphyrin is incorporated onto the IONP (ZnPR-IONP). On the other hand, the porphyrin derivative PR-TRIS3OH, incorporating several polar groups (TRIS), was synthesized and immobilized with the intention of obtaining water soluble nanosystems (PR-TRIS-IONP). When the singlet oxygen production ability was evaluated, the values obtained were similar to ZnPR-COOH/ZnPR-IONP, again much higher in the case of the nanoparticles PR-TRIS-IONP, with more than a twofold increase. The efficient singlet oxygen production of PR-TRIS-IONP together with their water solubility, points to the great promise that these new nanotools represent for PDT. PMID:26454374

  7. ZnO nanoparticles as drug delivery agent for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fakhar-e-Alam, M.; Rahim, S.; Atif, M.; Hammad Aziz, M.; Imran Malick, M.; Zaidi, S. S. Z.; Suleman, R.; Majid, A.

    2014-02-01

    Multidrug resistance (MDR) limits the success of many tumoricidal drugs. Non-significant accumulation of the drug into the target site is one major problem in photodynamic therapy. Nanoparticles are extensively used as efficient drug carriers in various local infectious and premalignant biological tissues. Due to their unique physical and chemical properties, PEGylated zinc oxide nanoparticles (ZnO NPs) exhibit high drug loading capacities, sustained drug release profiles and long-term anticancer efficacy. (Polyethylene glycol) PEG-zinc oxide nanoparticles were synthesized using the aquis chemical technique. Morphology/structural analysis of the said nanoparticles was confirmed by applying many techniques, e.g. scanning electron microscopy (SEM) and XRD. Average grain size of the nanoparticles, which was ≈100 nm, was calculated by applying the Scherrer formula. The PEGylated ZnO NPs were loaded with protoporphyrin IX (PpIX) to enhance the capability of drug carrying potency. Current work focused on the comparison of the cell killing effect (apoptosis/necrosis) by functionalizing different nanostructures via PEGylated ZnO NPs and bare ZnO NPs using the free-standing drug delivery procedure. ZnO NPs were used as anticancer drug vehicles because of their biocompatibility and bio-safety profile. The apoptotic effect of PEGylated tumoricidal drugs has been studied in human muscle carcinoma (RD cell line) in the dark as well as under laser exposure. It was concluded that PpIX localization was a significant time greater using encapsulation as compared to a conventional drug delivery system. This new technique may find excellent opportunities in the field of nanomedicine, especially in a multidrug delivery system.

  8. Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Shi, Changhong; Wu, Jason Boyang; Pan, Dongfeng

    2016-05-01

    A class of near-infrared fluorescence (NIRF) heptamethine cyanine dyes that are taken up and accumulated specifically in cancer cells without chemical conjugation have recently emerged as promising tools for tumor imaging and targeting. In addition to their fluorescence and nuclear imaging-based tumor-imaging properties, these dyes can be developed as drug carriers to safely deliver chemotherapy drugs to tumors. They can also be used as effective agents for photodynamic therapy with remarkable tumoricidal activity via photodependent cytotoxic activity. The preferential uptake of dyes into cancer but not normal cells is co-operatively mediated by the prevailing activation of a group of organic anion-transporting polypeptides on cancer cell membranes, as well as tumor hypoxia and increased mitochondrial membrane potential in cancer cells. Such mechanistic explorations have greatly advanced the current application and future development of NIRF dyes and their derivatives as anticancer theranostic agents. This review summarizes current knowledge and emerging advances in NIRF dyes, including molecular characterization, photophysical properties, multimodal development and uptake mechanisms, and their growing potential for preclinical and clinical use.

  9. Aminolevulinic Acid-Photodynamic Therapy Combined with Topically Applied Vascular Disrupting Agent Vadimezan Led to Enhanced Antitumor Responses

    PubMed Central

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor-vascular disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a non-invasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. Additionally, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA assays to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared to ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. PMID:21575001

  10. Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.

    PubMed

    Luiza Andreazza, Nathalia; Vevert-Bizet, Christine; Bourg-Heckly, Geneviève; Sureau, Franck; José Salvador, Marcos; Bonneau, Stephanie

    2016-08-20

    Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake. PMID:27282536

  11. 5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Wilson, Clara; Iyer, Karthik

    2011-02-01

    5-Fluorouracil (5-FU) was developed in the 1950s as an anticancer drug and is now widely used to treat many cancers, including colon and breast carcinoma. 5-FU causes fluoronucleotide misincorporation into RNA and DNA, inhibits thymidylate synthase, and leads to growth arrest and apoptosis. For skin precancers (actinic keratoses; AK), 5-FU is prescribed as a topical agent and was essentially the only option for treating widespread AK of the skin prior to FDA approval of photodynamic therapy (PDT) in 1999. PDT is now gradually replacing 5-FU as a preferred treatment for AK, but neither PDT nor 5-FU are effective for true skin cancers (basal or squamous cell), particularly for tumors >1 mm in depth. In our ongoing work to improve the efficacy of PDT for skin cancer, we previously showed that PDT efficacy can be significantly enhanced by preconditioning tumors with methotrexate (MTX), which leads to increased production of protoporphyrin IX (PpIX) in target cells. However, because MTX must be given orally or intravenously, it is considered unacceptable for widespread human use due to potential toxicity. MTX and 5-FU exert similar effects on the thymidylate synthesis pathway, so we reasoned that topical 5-FU could be a potential alternative to MTX. In this paper, exploratory studies that test 5-FU as a preconditioning agent for PDT are presented. In a cutaneous model of squamous cell carcinoma (chemically-induced papillomatous tumors in mice), 5-FU significantly enhances PpIX accumulation and therefore emerges as a new candidate agent for combination therapy with PDT.

  12. 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

  13. Enhancement of 5-aminolevulinic-acid-induced photodynamic therapy using light-dose fractionation and iron-chelating agents

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Postle-Hacon, Matthew J.; MacRobert, Alexander J.; Bown, Stephen G.

    1998-05-01

    Preliminary clinical studies of 5-aminolaevulinic acid (ALA) induced photodynamic therapy (PDT) with the maximum tolerated oral dose (60 mg/kg), currently appear to only produce limited amounts of necrosis. We have studied ways of increasing this effect without increasing the drug dose. In normal, female, Wistar rats we have found it possible to increase the area of necrosis produced in the colon substantially by simply interrupting the light dose (25 J, 635 nm, 100 mW) for a short period of time, while all other variables are kept constant. It is possible to cause up to four times more necrosis with a dose of 200 mg/kg ALA i.v. by introducing a single 150 second interval which splits the light dose into two fractions after 5 J has been delivered. We have found these parameters to be optimal for this dose. Likewise, in the same model, the effect of the iron chelating agent, CP94, was also investigated and we have found it possible to produce three times the area of necrosis with the simultaneous administration of 100 mg/kg CP94 i.v. and 50 mg/kg ALA i.v. We have therefore shown, that it is possible to significantly increase the effects of ALA induced PDT without increasing the administered dose of ALA by utilizing these techniques.

  14. 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.

  15. Current trends in outwitting resistance development in Candida infections through photodynamic and short peptide therapies: a strategic-shift from conventional antifungal agents.

    PubMed

    Louis, Bengyella; Waikhom, Sayanika Devi; Atadja, Peter W

    2016-01-01

    Disequilibrium in the human debilitated immune system favors proliferation of invasive Candida species, a major therapeutic challenge due to development of resistance to several conventional antifungal agents (CAA) worldwide. Multiple mutations observed at specific loci that are targets for CAA are recognized as sources of drug resistance. This has prompted a shift from CAA, to diverse combination therapies, photodynamic and short peptide therapies capable of triggering specific apoptotic reactions within candidal cells. In this review, new designs and combination of short peptide (SP) with CAA as well as current application of photodynamic inactivation (PDI) against Candida species geared at generating reactive species of oxygen (ROS) and nitrogen (RNS) are discussed. It is observed that oxidative and nitrosative stresses provides a superior broad candidacidal effects for eradication of drug-resistant Candida species. The mechanism and limitations in these strategic approaches over CAA is also discussed. PMID:26822688

  16. 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.

  17. 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

  18. Photosensitizer decorated iron oxide nanoparticles: bimodal agent for combined hyperthermia and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Yang, Zhimou; Xu, Keming; Zhang, Bei; Xu, Bing; Zhang, Xixiang; Chang, Chi K.

    2006-02-01

    As the PDT effect may be enhanced by localized hyperthermia (HT), it would be logical to find a single agent that could bring about these two modalities at precisely the target site for synergism. Since highly localized HT can be induced by magnetic field excitation of superparamagnetic nanoparticles, we report here the design and synthesis of photosensitizer-decorated iron oxide nanoparticles and their tumoricidal effect. Thus, a porphyrin is covalently anchored on the iron oxide nanoparticle via dihydroxybenzene which binds tightly on the surface of the nanoparticle by M-O bond. The morphology of the resultant nanoparticle was studied to show that the crystallinality is not changed and the nanoparticle remains superparamagnetic at room temperature. The conjugate is also strongly fluorescent indicating that the iron oxide hardly affects the optical properties of the surface bound porphyrin moieties. The conjugate is readily taken by cancer cell (Hela cell line) and is able to trigger apoptosis after excitation by light.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Metal-based phthalocyanines as a potential photosensitizing agent in photodynamic therapy for the treatment of melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maduray, Kaminee; Odhav, B.

    2014-03-01

    Photodynamic therapy (PDT) is an emerging medical treatment that uses photosensitizers (drug) which are activated by laser light for the generation of cytotoxic free radicals and singlet oxygen molecules that cause tumor cell death. In the recent years, there has been a focus on using and improving an industrial colorant termed phthalocyanines as a prospective photosensitizer because of its unique properties. This in vitro study investigated the photodynamic effect of indium (InPcCl) and iron (FePcCl) phthalocyanine chlorides on human skin cancer cells (melanoma). Experimentally, 2 x 104 cells/ml were seeded in 24-well tissue culture plates and allowed to attach overnight, after which cells were treated with different concentrations (2 μg/ml - 100 μg/ml) of InPcCl and FePcCl. After 2 h, cells were irradiated with constant light doses of 2.5 J/cm2, 4.5 J/cm2 and 8.5 J/cm2 delivered from a diode laser. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT Assay. At 24 h after PDT, irradiation with a light dose of 2.5 J/cm2 for each photosensitizing concentration of InPcCl and FePcCl produced a significant decrease in cell viability, but when the treatment light dose was further increased to 4.5 J/cm2 and 8.5 J/cm2 the cell survival was less than 55% for photosensitizing concentrations of InPcCl and FePcCl from 4 μg/ml to 100 μg/ml. This PDT study concludes that low concentrations on InPcCl and FePcCl activated with low level light doses can be used for the effective in vitro killing of melanoma cancer cells.

  4. 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.

  5. Development and characterization of bio-derived polyhydroxyalkanoate nanoparticles as a delivery system for hydrophobic photodynamic therapy agents.

    PubMed

    Pramual, Sasivimon; Assavanig, Apinya; Bergkvist, Magnus; Batt, Carl A; Sunintaboon, Panya; Lirdprapamongkol, Kriengsak; Svasti, Jisnuson; Niamsiri, Nuttawee

    2016-02-01

    In this study, we developed and investigated nanoparticles of biologically-derived, biodegradable polyhydroxyalkanoates (PHAs) as carriers of a hydrophobic photosensitizer, 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H, 23H-porphine (pTHPP) for photodynamic therapy (PDT). Three PHA variants; polyhydroxybutyrate, poly(hydroxybutyrate-co-hydroxyvalerate) or P(HB-HV) with 12 and 50% HV were used to formulate pTHPP-loaded PHA nanoparticles by an emulsification-diffusion method, where we compared two different poly(vinyl alcohol) (PVA) stabilizers. The nanoparticles exhibited nano-scale spherical morphology under TEM and hydrodynamic diameters ranging from 169.0 to 211.2 nm with narrow size distribution. The amount of drug loaded and the drug entrapment efficiency were also investigated. The in vitro photocytotoxicity was evaluated using human colon adenocarcinoma cell line HT-29 and revealed time and concentration dependent cell death, consistent with a gradual release pattern of pTHPP over 24 h. This study is the first demonstration using bacterially derived P(HB-HV) copolymers for nanoparticle delivery of a hydrophobic photosensitizer drug and their potential application in PDT. PMID:26712706

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. [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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma

    NASA Astrophysics Data System (ADS)

    Anand, Sanjay; Honari, Golara; Paliwal, Akshat; Hasan, Tayyaba; Maytin, Edward V.

    2009-06-01

    Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an emerging treatment for cancers. ALA, given as a prodrug, selectively accumulates and is metabolized in cancer cells to form protoporphyrin IX (PpIX). Targeted local irradiation with light induces cell death. Since the efficacy of ALA-PDT for large or deep tumors is currently limited, we are developing a new approach that combines differentiation-inducing agents with ALA-PDT to improve the clinical response. Here, we tested this new combination paradigm in the following two models of skin carcinoma in mice: 1) tumors generated by topical application of chemical carcinogens (DMBA-TPA); 2) human SCC cells (A431) implanted subcutaneously. To achieve a differentiated state of the tumors, pretreatment with a low concentration of methotrexate (MTX) or Vitamin D (Vit D) was administered for 72 h prior to exposure to ALA. Confocal images of histological sections were captured and digitally analyzed to determine relative PpIX levels. PpIX in the tumors was also monitored by real-time in vivo fluorescence dosimetry. In both models, a significant increase in levels of PpIX was observed following pretreatment with MTX or Vit D, as compared to no-pretreatment controls. This enhancing effect was observed at very low, non-cytotoxic concentrations, and was highly specific to cancer cells as compared to normal cells. These results suggest that use of differentiating agents such as MTX or Vit D, as a short-term combination therapy given prior to ALA-PDT, can increase the production of PpIX photosensitizer and enhance the therapeutic response of skin cancers.

  3. A Theranostic Agent Combining a Two-Photon-Absorbing Photosensitizer for Photodynamic Therapy and a Gadolinium(III) Complex for MRI Detection.

    PubMed

    Schmitt, Julie; Heitz, Valérie; Sour, Angélique; Bolze, Frédéric; Kessler, Pascal; Flamigni, Lucia; Ventura, Barbara; Bonnet, Célia S; Tóth, Éva

    2016-02-18

    The convergent synthesis and characterization of a potential theranostic agent, [DPP-ZnP-GdDOTA](-), which combines a diketopyrrolopyrrole-porphyrin component DPP-ZnP as a two-photon photosensitizer for photodynamic therapy (PDT) with a gadolinium(III) DOTA complex as a magnetic resonance imaging probe, is presented. [DPP-ZnP-GdDOTA](-) has a remarkably high longitudinal water proton relaxivity (19.94 mm(-1)  s(-1) at 20 MHz and 25 °C) for a monohydrated molecular system of this size. The Nuclear Magnetic Relaxation Dispersion (NMRD) profile is characteristic of slow rotation, related to the extended and rigid aromatic units integrated in the molecule and to self-aggregation occurring in aqueous solution. The two-photon properties were examined and large two-photon absorption cross-sections around 1000 GM were determined between 910 and 940 nm in DCM with 1 % pyridine and in DMSO. Furthermore, the new conjugate was able to generate singlet oxygen, with quantum yield of 0.42 and 0.68 in DCM with 1 % pyridine and DMSO, respectively. Cellular studies were also performed. The [DPP-ZnP-GdDOTA](-) conjugate demonstrated low dark toxicity and was able to induce high one-photon and moderate two-photon phototoxicity on cancer cells. PMID:26791109

  4. 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.

  5. 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

  6. 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

  7. 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

  8. In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rollakanti, K.; Anand, S.; Maytin, E. V.

    2013-03-01

    Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. [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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Poly(D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic therapy: enhancing singlet oxygen release and photototoxicity by surface PEG coating

    NASA Astrophysics Data System (ADS)

    Boix-Garriga, Ester; Acedo, Pilar; Casadó, Ana; Villanueva, Angeles; Stockert, Juan Carlos; Cañete, Magdalena; Mora, Margarita; Lluïsa Sagristá, Maria; Nonell, Santi

    2015-09-01

    Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are being considered as nanodelivery systems for photodynamic therapy. The physico-chemical and biological aspects of their use remain largely unknown. Herein we report the results of a study of PLGA NPs for the delivery of the model hydrophobic photosensitizer ZnTPP to HeLa cells. ZnTPP was encapsulated in PLGA with high efficiency and the NPs showed negative zeta potentials and diameters close to 110 nm. Poly(ethylene glycol) (PEG) coating, introduced to prevent opsonization and clearance by macrophages, decreased the size and zeta potential of the NPs by roughly a factor of two and improved their stability in the presence of serum proteins. Photophysical studies revealed two and three populations of ZnTPP and singlet oxygen in uncoated and PEGylated NPs, respectively. Singlet oxygen is confined within the NPs in bare PLGA while it is more easily released into the external medium after PEG coating, which contributes to a higher photocytotoxicity towards HeLa cells in vitro. PLGA NPs are internalized by endocytosis, deliver their cargo to lysosomes and induce cell death by apoptosis upon exposure to light. In conclusion, PLGA NPs coated with PEG show high potential as delivery systems for photodynamic applications.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Synthesis and characterization of NIR-responsive Aurod@pNIPAAm-PEGMA nanogels as vehicles for delivery of photodynamic therapy agents

    PubMed Central

    2013-01-01

    A near-infrared (NIR)-responsive Aurod@pNIPAAm-PEGMA nanogel was synthesized in two steps, growing a PEGMA monolayer on the surface of gold nanorods (AuNRs), followed by in situ polymerization and cross-linking of N-iso-propylacrylamide (NIPAAm) and poly-(ethylene glycol)-methacrylate (PEGMA). The AuNRs and Aurod@pNIPAAm-PEGMA nanogel were characterized by UV–vis spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy, respectively. The lower critical solution temperature of the Aurod@pNIPAAm-PEGMA nanogel could be tuned by changing the molar ratio of NIPAAm/PEGMA. The NIR-mediated drug release behavior of the Aurod@pNIPAAm-PEGMA nanogel was studied with zinc phthalocyanines (ZnPc4) as a drug model. It was also demonstrated that the loaded ZnPc4 could keep the capability of generating singlet oxygen, and the in vitro study showed a great photodynamic therapy (PDT) effect on Hela cells. It thus indicated the potential of this Aurod@pNIPAAm-PEGMA nanogel for application as a drug carrier in PDT, which might make contributions to oncotherapy. PMID:23279853

  19. Synthesis of poly(vinyl alcohol)/C(60) and poly(N-vinylpyrrolidone)/C(60) nanohybrids as potential photodynamic cancer therapy agents.

    PubMed

    Hurtgen, Marie; Debuigne, Antoine; Mouithys-Mickalad, Ange; Jérôme, Robert; Jérôme, Christine; Detrembleur, Christophe

    2010-04-01

    Well-defined poly(vinyl acetate) (PVAc) and poly(N-vinylpyrrolidone)-co-poly(vinyl acetate) (PNVP-co-PVAc) chains end-capped by Co(acac)(2) (acac=acetylacetonate) and prepared by cobalt-mediated radical polymerization (CMRP) are grafted onto a fullerene. Homolytic Co-C bond cleavage of the polymer chain ends at 30 degrees C releases the polymeric radicals that add onto C(60), thereby leading to the corresponding PVAc/C(60) and PNVP-co-PVAc/C(60) nanohybrids. The [polymer-Co(acac)(2)]/[C(60)] molar ratio was varied to adjust the structure of the nanohybrids, and more particularly the number of grafted arms. Finally, the potential of the hydrosoluble PVOH/C(60) nanohybrids, which result from the methanolysis of the ester groups of PVAc/C(60), and of the PNVP-co-PVAc/C(60) nanohybrids as photosensitizers for photodynamic therapy (PDT), was approached. First, photobleaching tests demonstrated the ability of these nanohybrids to produce singlet oxygen upon irradiation, which can play a role in cell damage. Second, cell viability assays demonstrated that both types of nanohybrids are deprived of intrinsic cytotoxicity in the dark, whereas they promoted significant cell mortality when subjected to light treatment. The selective response of these materials to irradiation makes them promising compounds for PDT. PMID:20140908

  20. 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.

  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. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Site-specific conjugation of single domain antibodies to liposomes enhances photosensitizer uptake and photodynamic therapy efficacy

    NASA Astrophysics Data System (ADS)

    Broekgaarden, M.; van Vught, R.; Oliveira, S.; Roovers, R. C.; van Bergen En Henegouwen, P. M. P.; Pieters, R. J.; van Gulik, T. M.; Breukink, E.; Heger, M.

    2016-03-01

    Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested.Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested. Electronic supplementary information (ESI) available: Materials and methods. See DOI: 10.1039/c6nr00014b

  9. 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.

  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. 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

  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. 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.

  14. [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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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) ).

  16. 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.

  17. 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

  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. 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

  20. [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

  1. 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

  2. Site-specific conjugation of single domain antibodies to liposomes enhances photosensitizer uptake and photodynamic therapy efficacy.

    PubMed

    Broekgaarden, M; van Vught, R; Oliveira, S; Roovers, R C; van Bergen En Henegouwen, P M P; Pieters, R J; Van Gulik, T M; Breukink, E; Heger, M

    2016-03-17

    Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested. PMID:26954515

  3. 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.

  4. 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-).

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Studying Light Propagation in Bone for Treatment of Bone Cancers with Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent; Gustafson, Scott; Jacques, Steven

    2008-05-01

    Photodynamic therapy makes use of light, photosensitizing agents, and oxygen as a selective means of treating cancer. The work presented is aimed at applying photodynamic therapy towards treatment of osteosarcoma in small animal clinics. To best facilitate clinical treatments, we must first understand how light propagates and how best to deliver adequate light to achieve phototoxic effects within bone. This work aims at characterizing how light propagates through bone and then applying that knowledge towards predicting light distributions in bone. Reflectance spectroscopy using an optical fiber source-collector pair is used to determine the scattering properties of bone tissues, and the absorption due to water and oxygenated and deoxygenated hemoglobin---native absorbers at visible and near-IR wavelengths. Resulting optical characterizations are then applied to a cylindrically symmetric Monte Carlo model in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  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. Photosensitizer-Conjugated Silica-Coated Gold Nanoclusters for Fluorescence Imaging-Guided Photodynamic Therapy

    PubMed Central

    Huang, Peng; Lin, Jing; Wang, Shouju; Zhou, Zhijun; Li, Zhiming; Wang, Zhe; Zhang, Chunlei; Yue, Xuyi; Niu, Gang; Yang, Min; Cui, Daxiang; Chen, Xiaoyuan

    2013-01-01

    Multifunctional theranostics have recently been intensively explored to optimize the efficacy and safety of therapeutic regimens. In this work, a photo-theranostic agent based on chlorin e6 (Ce6) photosensitizer-conjugated silica-coated gold nanoclusters (AuNCs@SiO2-Ce6) is strategically designed and prepared for fluorescence imaging-guided photodynamic therapy (PDT). The AuNCs@SiO2-Ce6 shows the following features: i) high Ce6 photosensitizer loading; ii) no non-specific release of Ce6 during its circulation; iii) significantly enhanced cellular uptake efficiency of Ce6, offering a remarkably improved photodynamic therapeutic efficacy compared to free Ce6; iv) subcellular characterization of the nanoformula via both the fluorescence of Ce6 and plasmon luminescence of AuNCs; v) fluorescence imaging-guided photodynamic therapy (PDT). This photo-theranostics owns good stability, high water dispersibility and solubility, non-cytotoxicity, and good biocompatibility, thus facilitating its biomedical applications, particularly for multi-modal optical, CT and photoacoustic (PA) imaging guided PDT or sonodynamic therapy. PMID:23523428

  17. 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

  18. 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

  19. 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

  20. Cucurbit[8]uril Regulated Activatable Supramolecular Photosensitizer for Targeted Cancer Imaging and Photodynamic Therapy.

    PubMed

    Wang, Xiao-Qiang; Lei, Qi; Zhu, Jing-Yi; Wang, Wen-Jing; Cheng, Qian; Gao, Fan; Sun, Yun-Xia; Zhang, Xian-Zheng

    2016-09-01

    Activatable photosensitizers (aPSs) have emerged as promising photodynamic therapy (PDT) agents for simultaneous imaging and selective ablation of cancer. However, traditional synthetic aPSs are limited by complex design and tedious synthesis. Here, aPS regulated by cucurbit[8]uril (CB[8]) for targeted cancer imaging and PDT is reported. This system is based on the host-guest interaction between biotinylated toluidine blue (TB-B) and CB[8] to form 2TB-B@CB[8]. Moreover, a facile strategy to turn off/on the fluorescence and photodynamic activity of TB-B is developed through the reversible assembly/disassembly of 2TB-B@CB[8]. This established system can achieve selective accumulation in tumor, light-up cancer imaging, and enhanced anticancer behavior. Therefore, this work provides a novel and promising strategy for the aPS build via simple and facile regulation of supramolecular chemistry. PMID:27513690

  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. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  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. 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

  10. 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).

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2015-11-01

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

  14. 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.

  15. "Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.

    PubMed

    Bano, Shazia; Nazir, Samina; Munir, Saeeda; AlAjmi, Mohamed Fahad; Afzal, Muhammad; Mazhar, Kehkashan

    2016-01-01

    We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy. PMID:27471383

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  18. 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

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

    PubMed

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

    2015-06-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  6. 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%.

  7. 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.

  8. 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

  9. 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

  10. Two-photon excitation of chlorin-e6-C15 monomethyl ester for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Chen, Ping; Zhao, P. D.; Guo, P.; Lin, Lie; Liu, J. Wei; Yu, Q.

    2005-01-01

    Two-photon-induced fluorescence spectrum and lifetime of Chlorin-e6-C15 Monomethyl Ester in tetrahydrofura (THF) are experimentally examined with femtosecond laser pulses at 800 nm from a Ti:sapphire laser. The two-photon excited fluorescence spectra of the molecule are basically similar to those obtained by one-photon excitation. The lifetimes of two-photon and one-photon excitation fluorescence of this molecule in the solution are of the order of 5.2 ns and 4.8 ns respectively. Our experimental results indicate that the two-photon-induced photodynamic processes of Chlorin-e6-C15 Monomethyl Ester are similar to one-photon-induced photodynamic processes. The two-photon absorption cross section of the molecule is measured at 800 nm as about σ2' ~ 29.1 x 10-50 cm4 " s/photon. As an example for two-photon photodynamic therapy, we also further examine the cell-damaging effects of the Ester. Our preliminary results of cell viability test indicate that Chlorin-e6-C15 Monomethyl Ester can effectively damage the liver cancer cells BEL-7402 under two-photon irradiation. Our results suggest Chlorin-e6-C15 Monomethyl Ester may become a potential two-photon phototherapeutic agent.

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

    PubMed

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

    2014-07-21

    Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a β-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy. PMID:24933297

  12. A Mitochondria-Targeted Photosensitizer Showing Improved Photodynamic Therapy Effects Under Hypoxia.

    PubMed

    Lv, Wen; Zhang, Zhang; Zhang, Kenneth Yin; Yang, Huiran; Liu, Shujuan; Xu, Aqiang; Guo, Song; Zhao, Qiang; Huang, Wei

    2016-08-16

    Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy. PMID:27381490

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Autologous bone marrow transplantation by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  3. 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.

  4. 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.

  5. 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

  6. Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Z.; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

    2016-03-01

    We introduce photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage in synchrony with photo-initiation of tumor-confined, multikinase inhibitor release. The PMIL is a biodegradable delivery system comprised of a nanoliposome carrying a photoactivable chromophore (benzoporphyrin derivative monoacid A, BPD) in its bilayer. A multikinase inhibitor-loaded PEG-PLGA nanoparticle is encapsulated within the liposome, which acts a barrier to nanoparticle erosion and drug release. Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates tumor-confined drug release from the nanoparticle. This talk presents promising preclinical data in mouse models of pancreatic cancer utilizing this concept to suppress the VEGF and MET signaling pathways—both critical to cancer progression, metastasis and treatment escape. A single PMIL treatment using low doses of a multikanse inhibitor (cabozantinib, XL184) achieves sustained tumor reduction and suppresses metastatic escape, whereas combination therapy by co-administration of the individual agents has significantly reduced efficacy. The PMIL concept is amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies whilst reducing systemic drug exposure and associated toxicities.

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

    NASA Astrophysics Data System (ADS)

    Cohen, Brian A.

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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P < 0.01), there is a significant statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  13. Photochemical predictive analysis of photodynamic therapy with non-homogeneous topical photosensitizer distribution in dermatological applications

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

    Photodynamic Therapy (PDT) is a therapeutic technique widely used in dermatology to treat several skin pathologies. It is based in topical or systemic delivery of photosensitizing drugs followed by irradiation with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell necrosis. In this work we present a PDT model that tries to predict the photodynamic effect on the skin with a topically administered photosensitizer. The time dependent inhomogeneous distribution of the photoactive compound protoporphyrin IX (PpIX) is calculated after obtaining its precursor distribution (Methyl aminolevulinate, MAL) which depends on the drug permeability, diffusion properties of the skin, incubation time and conversion efficiency of MAL to PpIX. Once the optical energy is obtained by means of the Beer Lambert law, a photochemical model is employed to estimate the concentration of the different molecular compounds taking into account the electronic transitions between molecular levels and particles concentrations. The results obtained allow us to know the evolution of the cytotoxic agent in order to estimate the necrotic area adjusting parameters such as the optical power, the photosensitizer concentration, the incubation and exposition time or the diffusivity and permeability of the tissue.

  14. Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Kopelman, Raoul

    2008-03-01

    Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

  15. Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy.

    PubMed

    Huang, Huaiyi; Yu, Bole; Zhang, Pingyu; Huang, Juanjuan; Chen, Yu; Gasser, Gilles; Ji, Liangnian; Chao, Hui

    2015-11-16

    Photodynamic therapy (PDT) is a noninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer. However, the currently clinically used PDT agents have several limitations, such as low water solubility, poor photostability, and limited selectivity towards cancer cells, aside from having very low two-photon cross-sections around 800 nm, which limits their potential use in TP-PDT. To tackle these drawbacks, three highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localize in the lysosomes, an ideal localization for PDT purposes. One of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy. PMID:26447888

  16. 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.

  17. 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

  18. Comparison of two photosensitizers in photodynamic therapy using light pulses in femtosecond regime: an animal study

    NASA Astrophysics Data System (ADS)

    Grecco, Clóvis; Pratavieira, Sebastião.; Bagnato, Vanderlei; Kurachi, Cristina

    2016-03-01

    Photodynamic therapy is a therapeutic modality for cancer treatment based on the interaction of light with a sensitizer agent and molecular oxygen present into the target cells. The aim of this study is the evaluation of photodynamic therapy using pulsed light source in the femtosecond regime through necrosis induced in healthy rat liver. The induced necrosis profile with CW laser and pulsed laser were evaluated in animal model, which received Photodithazine (chlorine e6 derivative). The light sources used in these studies were a 660 nm CW diode laser and a Ti:Sapphire Regenerative Amplifier laser (1 kHz repetition rate and 100 fs pulse width) associated with an optical parametric amplifier (OPA) to convert to 660 nm. The results were compared with a previous study when was used a hematoporphyrin derivative (Photogem) as a sensitizer. The induced necrosis with Photogen was greater with pulsed laser (2.0 +/- 0.2 mm) in comparison with CW laser (1.0 ± 0.2 mm), while in Photodithazine the induced necrosis with was greater with CW laser (2.9 +/- 0.2 mm) comparing the pulsed laser (2.0 +/- 0.2 mm). These results indicate dependence of PDT mechanisms with photosensitizer and the light regime applied.

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  20. Enhanced Fluorescence Imaging Guided Photodynamic Therapy of Sinoporphyrin Sodium Loaded Graphene Oxide

    PubMed Central

    Yan, Xuefeng; Niu, Gang; Lin, Jing; Jin, Albert J.; Hu, Hao; Tang, Yuxia; Zhang, Yujie; Wu, Aiguo; Lu, Jie; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

    2014-01-01

    Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by π-π stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits this GO-PS system for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT. The fluorescence of loaded DVDMS is drastically enhanced via intramolecular charge transfer. Meanwhile, the GO-PEG vehicles can significantly increase the tumor accumulation efficiency of DVDMS and lead to an improved photodynamic therapy (PDT) efficacy as compared to DVDMS alone. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. Most intriguingly, 100% in vivo tumor elimination was achieved by intravenous injection of GO-PEG-DVDMS (2 mg/kg of DVDMS, 50 J) without tumor recurrence, loss of body weight or other noticeable toxicity. This novel GO-PEG-DVDMS theranostics is well suited for enhanced fluorescence imaging guided PDT. PMID:25542797

  1. 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%.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Gold nanorod-photosensitizer complex obtained by layer-by-layer method for photodynamic/photothermal therapy in vitro.

    PubMed

    Kim, Seung Beom; Lee, Tae Heon; Yoon, Il; Shim, Young Key; Lee, Woo Kyoung

    2015-03-01

    Gold nanorod (GNR)-photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin-18) and cationic poly(allylamine hydrochloride) by layer-by-layer method, and was characterized by transmission electron microscopy, UV-vis spectroscopy, and zeta potential. The GNR-PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT. PMID:25630881

  9. 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

  10. 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.

  11. 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

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  15. Innovative drug delivery strategies for topical photodynamic therapy using porphyrin precursors.

    PubMed

    Morrow, Desmond I J; Garland, Martin J; McCarron, Paul A; Woolfson, A David; Donnelly, Ryan F

    2007-01-01

    Photodynamic therapy (PDT) has been extensively investigated as a treatment for tumors and neoplasias of the skin, bladder, mouth, and female reproductive tract. The most convenient drug delivery route, when focusing on the photodynamic treatment of such tumors and neoplasia, is the transdermal. However, with the inherent "barrier function" of the stratum corneum of the skin, drugs with high molecular weight (> 500 Daltons) or extremes of polarity will find it difficult to successfully cross the skin. Therefore, preformed photosensitizers, which are generally large, highly conjugated molecules, are not commonly used in topical PDT. This has led to the idea of endogenous photosensitization using the small (167.8 Daltons), although hydrophilic, 5-aminolevulinic acid (ALA) being the most frequently employed agent in modern topical PDT. Although clinical application of ALA and its bimolecular effects within target cells remain as primary research themes, the design and evaluation of delivery systems required for effective photosensitizer administration have been less well addressed. This paper briefly reviews traditional approaches to topical delivery of ALA and its esters, and highlights several innovative strategies recently employed to increase the efficacy of ALA-PDT. PMID:17725536

  16. Multifunctional poly (lactide-co-glycolide) nanoparticles for luminescence/magnetic resonance imaging and photodynamic therapy.

    PubMed

    Lee, Dong Jin; Park, Ga Young; Oh, Kyung Taek; Oh, Nam Muk; Kwag, Dong Sup; Youn, Yu Seok; Oh, Young Taik; Park, Jin Woo; Lee, Eun Seong

    2012-09-15

    Poly (lactide-co-glycolide) (PLGA) coupled with methoxy poly (ethylene glycol) (mPEG) or chlorin e6 (Ce6) was synthesized using the Steglich esterification method. PLGA-linked mPEG (PLGA-mPEG), PLGA-linked Ce6 (PLGA-Ce6), and Fe(3)O(4) were utilized to constitute multifunctional PLGA nanoparticles (∼160 nm) via the multi-emulsion W(1)/O/W(2) (water-in-oil-in-water) method. The photo-sensitizing properties of Ce6 molecules anchored to PLGA nanoparticles enabled in vivo luminescence imaging and photodynamic therapy for the tumor site. The encapsulation of Fe(3)O(4) allowed high contrast magnetic resonance (MR) imaging of the tumor in vivo. Overall, PLGA nanoparticles resulted in a significant tumor volume regression for the light-illuminated KB tumor in vivo and enhanced the contrast at the tumor region, compared to that of Feridex(®) (commercial contrast agent). PMID:22664459

  17. Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations.

    PubMed

    Mazzone, Gloria; Alberto, Marta E; De Simone, Bruna C; Marino, Tiziana; Russo, Nino

    2016-01-01

    The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600-800 nm). The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (Foscan©) already used in the photodynamic therapy (PDT) protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents. PMID:26938516

  18. Cancer treatment by photodynamic therapy combined with NK-cell-line-based adoptive immunotherapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai

    1998-05-01

    Treatment of solid cancers by photodynamic therapy (PDT) triggers a strong acute inflammatory reaction localized to the illuminated malignant tissue. This event is regulated by a massive release of various potent mediators which have a profound effect not only on local host cell populations, but also attract different types of immune cells to the treated tumor. Phagocytosis of PDT-damaged cancerous cells by antigen presenting cells, such as activated tumor associated macrophages, enables the recognition of even poorly immunogenic tumors by specific immune effector cells and the generation of immune memory populations. Because of its inflammatory/immune character, PDT is exceptionally responsive to adjuvant treatments with various types of immunotherapy. Combining PDT with immuneactivators, such as cytokines or other specific or non-specific immune agents, rendered marked improvements in tumor cures with various cancer models. Another clinically attractive strategy is adoptive immunotherapy, and the prospects of its use in conjunction with PDT are outlined.

  19. Spectroscopical study of bacteriopurpurinimide-naphthalimide conjugates for fluorescent diagnostics and photodynamic therapy.

    PubMed

    Panchenko, Pavel A; Sergeeva, Antonina N; Fedorova, Olga A; Fedorov, Yuri V; Reshetnikov, Roman I; Schelkunova, Anastasiya E; Grin, Mikhail A; Mironov, Andrey F; Jonusauskas, Gediminas

    2014-04-01

    Two novel bis(chromophoric) dyads ABPI-NI1 and ABPI-NI2 containing 1,8-naphthalimide and bacteriopurpurinimide units linked by p-phenylene-methylene (ABPI-NI1) and pentamethylene (ABPI-NI2) spacers were prepared to test their ability to be used in the design of effective agents for both photodynamic therapy (PDT) and fluorescent tumor imaging. Photophysical studies revealed that the emission from the naphthalimide chromophore in both conjugates was partially quenched due to resonance energy transfer between the photoactive components. Compound ABPI-NI2 with more sterically flexible oligomethylene group demonstrated higher fluorescence intensity as compared with that for ABPI-NI1. PMID:24727406

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

    PubMed

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

    2016-02-01

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

  17. 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.

  18. 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

  19. [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

  20. 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

  1. Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Spring, Bryan; Mai, Zhiming; Rai, Prakash; Chang, Sung; Hasan, Tayyaba

    2010-02-01

    Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the "right place at the right time". This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

  2. Endoscopic laser therapy in malignant tracheobronchial obstruction using sequential Nd YAG laser and photodynamic therapy

    PubMed Central

    Moghissi, K.; Dixon, K.; Hudson, E.; Stringer, M.; Brown, S.

    1997-01-01

    BACKGROUND: Because the survival after treatment of advanced inoperable endo-tracheobronchial carcinoma is so poor, a pilot study was undertaken to evaluate the combined cumulative effect on survival of neodymium yttrium aluminium garnet (Nd YAG) laser followed by photodynamic treatment used endoscopically. METHODS: Seventeen patients who presented between January 1992 and March 1996 with inoperable tracheobronchial lesions causing more than 50% endoluminal obstruction were selected to enter the pilot study. Initially they had bronchoscopic Nd YAG laser treatment to debulk the tumour, and this was followed six weeks later by photodynamic therapy to treat the residual tumour. RESULTS: All patients had symptomatic relief and at least a partial response, and seven had a complete response for 3-6 months. Eight of the 17 (47%) survived for at least two years and 11 (65%) survived for a year or more. The median survival of the 10 patients who had died by the time of writing was 18.5 months (range 5-39), 95% confidence interval (CI) 9.9 to 29.5. CONCLUSIONS: Combined Nd YAG laser and endoscopic photodynamic therapy may be an effective palliative treatment for patients with inoperable endotracheobronchial cancer. 


 PMID:9093347

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  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. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. “Smart” nickel oxide based core–shell nanoparticles for combined chemo and photodynamic cancer therapy

    PubMed Central

    Bano, Shazia; Nazir, Samina; Munir, Saeeda; AlAjmi, Mohamed Fahad; Afzal, Muhammad; Mazhar, Kehkashan

    2016-01-01

    We report “smart” nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm2, at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy. PMID:27471383

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. The effect of motexafin gadolinium on ALA photodynamic therapy in glioma spheroids

    NASA Astrophysics Data System (ADS)

    Mathews, Marlon S.; Sanchez, Rogelio; Sun, Chung-Ho; Madsen, Steen J.; Hirschberg, Henry

    2008-02-01

    Following surgical removal of malignant brain tumors 80% of all cases develop tumor recurrence within 2 cm of the resected margin. The aim of postoperative therapy is therefore elimination of nests of tumor cells remaining in the margins of the resection cavity. Light attenuation in tissue makes it difficult for adequate light fluences to reach depths of 1-2 cm in the resection margin making it difficult for standard intraoperative photodynamic therapy (PDT) to accomplish this goal. Thus additional agents are required that either increase the efficacy of low fluence PDT or inhibit cellular repair, to enhance effectiveness of PDT in the tumor resection cavity. Motexafin gadolinium (MGd) is one such agent previously reported to enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents by causing redox stress to cancerous cells. MGd is well tolerated with tumor specific uptake in clinical studies. The authors evaluated MGd as a potential PDT enhancing agent at low light fluences using an in vitro model. Multicellular Glioma spheroids (MGS) of approximately 300 micron diameter, obtained from ACBT cell lines were subjected to acute PDT treatments at 6J, 12J, and 18J light fluences. Growth was determined by measuring diameters in two axes. At four weeks a dose dependent inhibition of spheroid growth was seen in 33%, 55%, and 83% of the MGS at 6J, 12J, and 18J respectively, while inhibition followed by a partial reversal of growth was seen in 17%, 33%, and 17% respectively. This study provides a rationale for the use of this drug as a PDT enhancer in the management of brain tumors.

  11. Recent Progress in Chemical Modifications of Chlorophylls and Bacteriochlorophylls for the Applications in Photodynamic Therapy.

    PubMed

    Staron, Jakub; Boron, Bożena; Karcz, Dariusz; Szczygieł, Małgorzata; Fiedor, Leszek

    2015-01-01

    Since photodynamic therapy emerged as a promising cancer treatment, the development of photosensitizers has gained great interest. In this context, the photosynthetic pigments, chlorophylls and bacteriochlorophylls, as excellent natural photosensitizers, attracted much attention. In effect, several (bacterio) chlorophyll-based phototherapeutic agents have been developed and (or are about to) enter the clinics. The aim of this review article is to give a survey of the advances in the synthetic chemistry of these pigments which have been made over the last decade, and which are pertinent to the application of their derivatives as photosensitizers for photodynamic therapy (PDT). The review focuses on the synthetic strategies undertaken to obtain novel derivatives of (bacterio)chlorophylls with both enhanced photosensitizing and tumorlocalizing properties, and also improved photo- and chemical stability. These include modifications of the C- 17-ester moiety, the isocyclic ring, the central binding pocket, and the derivatization of peripheral functionalities at the C-3 and C-7 positions with carbohydrate-, peptide-, and nanoparticle moieties or other residues. The effects of these modifications on essential features of the pigments are discussed, such as the efficiency of reactive oxygen species generation, photostability, phototoxicity and interactions with living organisms. The review is divided into several sections. In the first part, the principles of PDT and photosensitizer action are briefly described. Then the relevant photophysical features of (bacterio)chlorophylls and earlier approaches to their modification are summarized. Next, a more detailed overview of the progress in synthetic methods is given, followed by a discussion of the effects of these modifications on the photophysics of the pigments and on their biological activity. PMID:26282940

  12. Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions

    SciTech Connect

    Tirand, Loraine; Bastogne, Thierry; Bechet, Denise M.Sc.; Linder, Michel; Thomas, Noemie; Frochot, Celine; Guillemin, Francois; Barberi-Heyob, Muriel

    2009-09-01

    Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm{sup 2}; fluence rate, 85 mW/cm{sup 2}). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent. Conclusions: Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.

  13. 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

    model for one of the possible mechanisms of synergistic interaction between photodynamic therapy and hyperthermia in cancer treatment. PMID:1828665

  14. Dual-Modality Positron Emission Tomography/Optical Image-Guided Photodynamic Cancer Therapy with Chlorin e6-Containing Nanomicelles.

    PubMed

    Cheng, Liang; Kamkaew, Anyanee; Sun, Haiyan; Jiang, Dawei; Valdovinos, Hector F; Gong, Hua; England, Christopher G; Goel, Shreya; Barnhart, Todd E; Cai, Weibo

    2016-08-23

    Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise in nanomedicine. Herein, we develop an organic photodynamic therapy (PDT) system based on polyethylene glycol (PEG)-coated nanomicelles conjugated with ∼20% chlorin e6 (PEG-Ce 6 nanomicelles), which functions as an optical imaging agent, as well as a PDT agent. The formed PEG-Ce 6 nanomicelles with the size of ∼20 nm were highly stable in various physiological solutions for a long time. Moreover, Ce 6 can also be a (64)Cu chelating agent for in vivo positron emission tomography (PET). By simply mixing, more than 90% of (64)Cu was chelator-free labeled on PEG-Ce 6 nanomicelles, and they also showed high stability in serum conditions. Both fluorescence imaging and PET imaging revealed that PEG-Ce 6 nanomicelles displayed high tumor uptake (13.7 ± 2.2%ID/g) after intravenous injection into tumor-bearing mice at the 48 h time point. In addition, PEG-Ce 6 nanomicelles exhibited excellent PDT properties upon laser irradiation, confirming the theranostic properties of PEG-Ce 6 nanomicelles for imaging and treatment of cancer. In addition, PDT was not shown to render any appreciable toxicity. This work presents a theranostic platform based on polymer nanomicelles with great potential in multimodality imaging-guided photodynamic cancer therapy. PMID:27459277

  15. Photodynamic Therapy: Occupational Hazards and Preventative Recommendations for Clinical Administration by Healthcare Providers

    PubMed Central

    Lacey, Steven E.; Vesper, Benjamin J.; Paradise, William A.; Radosevich, James A.; Colvard, Michael D.

    2013-01-01

    Abstract Objective: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. Materials and methods: Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. Results: Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. Conclusions: Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies. PMID:23859750

  16. Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp.

    PubMed Central

    Gao, Lujuan; Jiang, Shaojie; Sun, Yi; Deng, Meiqi; Wu, Qingzhi; Li, Ming; Zeng, Tongxiang

    2016-01-01

    Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm2), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in SMIC

  17. Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp.

    PubMed

    Gao, Lujuan; Jiang, Shaojie; Sun, Yi; Deng, Meiqi; Wu, Qingzhi; Li, Ming; Zeng, Tongxiang

    2016-01-01

    Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm(2)), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in

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

    PubMed

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

    2013-06-10

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

  19. Immunotherapy regimens for combination with photodynamic therapy aimed at eradication of solid cancers

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    2000-06-01

    Due to inflammatory/immune responses elicited by photodynamic therapy (PDT), this modality is particularly suitable in combination with various forms of immunotherapy for an improved therapeutic gain. A wide variety of approaches that may be applicable in this context include those focusing on amplifying the activity of particular immune cell types (neutrophils, macrophages, dendritic cells, natural killer cells, helper or cytotoxic T lymphocytes). Another type of approach is to focus on a specific phase of immune response development, which comprises the activation of non-specific inflammatory immune effectors, immune recognition, immune memory, immune rejection, or blocking of immune suppression. These different strategies call for a variety of immunotherapeutic protocols to be employed in combination with PDT. These include treatments such as: (1) non-specific immunoactivators (e.g. bacterial vaccines), (2) specific immune agents (cytokines, or other activating factors), (3) adoptive immunotherapy treatments (transfer of dendritic cells, tumor-sensitized T lymphocytes or natural killer cells), or (4) their combinations. Techniques of gene therapy employed in some of these protocols offer novel opportunities for securing a potent and persistent immune activity. Using PDT and immunotherapy represents an attractive combination for cancer therapy that is capable of eradicating both localized and disseminated malignant lesions.

  20. Photosensitizer-doped conjugated polymer nanoparticles for simultaneous two-photon imaging and two-photon photodynamic therapy in living cells

    NASA Astrophysics Data System (ADS)

    Shen, Xiaoqin; Li, Lin; Wu, Hao; Yao, Shao Q.; Xu, Qing-Hua

    2011-12-01

    Photosensitizer doped conjugated polymer nanoparticles have been prepared by incorporating polyoxyethylene nonylphenylether (CO-520) into the nanoparticles using a re-precipitation method. The conjugated polymer, poly[9,9-dibromohexylfluorene-2,7-ylenethylene-alt-1,4-(2,5-dimethoxy)phenylene] (PFEMO), was used as the host matrix to disperse tetraphenylporphyrin (TPP) and an energy donor to enhance the two-photon excitation properties of TPP. These CO-520 incorporated, TPP-doped PFEMO nanoparticles are stable and have low cytotoxicity in the dark. The TPP emission of the nanoparticles was found to be enhanced by about 20 times by PFEMO under two-photon excitation. The nanoparticles showed significantly enhanced two-photon excitation singlet oxygen generation efficiency and two-photon photodynamic therapy activity in cancer cells. These composite nanoparticles display features required for ideal photosensitizers, such as low cytotoxicity in the dark and efficient two-photon photodynamic activity under laser radiation. In addition, these novel nano-photosensitizers allow simultaneous in vivo monitoring by two-photon fluorescence imaging during two-photon photodynamic treatment. These photosensitizer-doped conjugated polymer nanoparticles can act as novel photosensitizing agents for two-photon photodynamic therapy and related applications.Photosensitizer doped conjugated polymer nanoparticles have been prepared by incorporating polyoxyethylene nonylphenylether (CO-520) into the nanoparticles using a re-precipitation method. The conjugated polymer, poly[9,9-dibromohexylfluorene-2,7-ylenethylene-alt-1,4-(2,5-dimethoxy)phenylene] (PFEMO), was used as the host matrix to disperse tetraphenylporphyrin (TPP) and an energy donor to enhance the two-photon excitation properties of TPP. These CO-520 incorporated, TPP-doped PFEMO nanoparticles are stable and have low cytotoxicity in the dark. The TPP emission of the nanoparticles was found to be enhanced by about 20 times by PFEMO

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    PubMed Central

    Olivo, Malini; Bhuvaneswari, Ramaswamy; Lucky, Sasidharan Swarnalatha; Dendukuri, Nagamani; Thong, Patricia Soo-Ping

    2010-01-01

    Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS), which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS), that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  16. 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

  17. New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy

    PubMed Central

    Kamarulzaman, Ezatul Ezleen; Mohd Gazzali, Amirah; Acherar, Samir; Frochot, Céline; Barberi-Heyob, Muriel; Boura, Cédric; Chaimbault, Patrick; Sibille, Estelle; Wahab, Habibah A.; Vanderesse, Régis

    2015-01-01

    Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide–PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent. PMID:26473840

  18. New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy.

    PubMed

    Kamarulzaman, Ezatul Ezleen; Gazzali, Amirah Mohd; Acherar, Samir; Frochot, Céline; Barberi-Heyob, Muriel; Boura, Cédric; Chaimbault, Patrick; Sibille, Estelle; Wahab, Habibah A; Vanderesse, Régis

    2015-01-01

    Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent. PMID:26473840

  19. Water-soluble benzylidene cyclopentanone based photosensitizers for in vitro and in vivo antimicrobial photodynamic therapy

    PubMed Central

    Fang, Yanyan; Liu, Tianlong; Zou, Qianli; Zhao, Yuxia; Wu, Feipeng

    2016-01-01

    Antimicrobial photodynamic therapy (aPDT) has been proposed to cope with the increasing antibiotic resistance among pathogens. As versatile pharmacophores, benzylidene cyclopentanone based photosensitizers (PSs) have been used in various bioactive materials. However, their reports as aPDT agents are very limited, and relationships between their chemical structures and antibacterial abilities have not been systematically discussed. Here, nine water-soluble benzylidene cyclopentanone PSs modified by polyethylene glycol (PEG), carboxylate anionic or pyridyl cationic agents are studied for aPDT. It is found that the binding/uptake abilities and aPDT effects of these PSs toward bacterial cells vary significantly when adjusting the number and position of their terminal charged groups. Though the comparable (also best) binding/uptake amounts are achieved by both cationic PS P3 and anionic PS Y1, only Y1 exhibits much more excellent aPDT activities than other PSs. Antibacterial mechanisms reveal that, relative to the favorable cell wall-binding of cationic PS P3, the anionic PS Y1 can accumulate more in the spheroplast/protoplast of methicillin-resistant Staphylococcus aureus (MRSA), which ensures its high efficient aPDT abilities both in vitro and in vivo. This study suggests the great clinical application potential of Y1 in inactivation of MRSA. PMID:27323899

  20. Water-soluble benzylidene cyclopentanone based photosensitizers for in vitro and in vivo antimicrobial photodynamic therapy.

    PubMed

    Fang, Yanyan; Liu, Tianlong; Zou, Qianli; Zhao, Yuxia; Wu, Feipeng

    2016-01-01

    Antimicrobial photodynamic therapy (aPDT) has been proposed to cope with the increasing antibiotic resistance among pathogens. As versatile pharmacophores, benzylidene cyclopentanone based photosensitizers (PSs) have been used in various bioactive materials. However, their reports as aPDT agents are very limited, and relationships between their chemical structures and antibacterial abilities have not been systematically discussed. Here, nine water-soluble benzylidene cyclopentanone PSs modified by polyethylene glycol (PEG), carboxylate anionic or pyridyl cationic agents are studied for aPDT. It is found that the binding/uptake abilities and aPDT effects of these PSs toward bacterial cells vary significantly when adjusting the number and position of their terminal charged groups. Though the comparable (also best) binding/uptake amounts are achieved by both cationic PS P3 and anionic PS Y1, only Y1 exhibits much more excellent aPDT activities than other PSs. Antibacterial mechanisms reveal that, relative to the favorable cell wall-binding of cationic PS P3, the anionic PS Y1 can accumulate more in the spheroplast/protoplast of methicillin-resistant Staphylococcus aureus (MRSA), which ensures its high efficient aPDT abilities both in vitro and in vivo. This study suggests the great clinical application potential of Y1 in inactivation of MRSA. PMID:27323899

  1. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  2. Photosensitizer cross-linked nano-micelle platform for multimodal imaging guided synergistic photothermal/photodynamic therapy.

    PubMed

    Liu, Xiaodong; Yang, Guangbao; Zhang, Lifen; Liu, Zhuang; Cheng, Zhenping; Zhu, Xiulin

    2016-08-18

    The multifunctional nano-micelle platform holds great promise to enhance the accuracy and efficiency of cancer diagnosis and therapy. In this work, an amphiphilic poly[(poly(ethylene glycol) methyl ether methacrylate)-co-(3-aminopropyl methacrylate)]-block-poly(methyl methacrylate) (P(PEGMA-co-APMA)-b-PMMA) block copolymer was synthesized by successive RAFT polymerizations and subsequent chemical modification. Then the multifunctional micelles with high solubility in physiological environments were developed by a self-assembly and crosslinking processes. The photosensitizer segment, 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP), serves as a tetra-functional cross-linker, photodynamic agent, fluorescence indicator, as well as magnetic resonance (MR) contrast agent after labelling with manganese ions (Mn(2+)), while IR825 simultaneously locating in the interior of the fabricated micelles contributed to the photoacoustic (PA) imaging ability and the photothermal effect. The prepared nanoparticles show great stability in a physiological environment with uniform morphology and diameters of around 80 nm as disclosed by stability investigation, TEM and DLS analysis. IR825@P(PEGMA-co-APMA)-b-PMMA@TCPP/Mn nanoparticles displayed high in vivo tumor uptake with a long blood circulation half-life (∼3.64 h) by the EPR effect after intravenous (i.v.) injection, as revealed by fluorescence, MR and PA imaging models. In vivo anti-tumor effects were achieved via a combined photothermal and photodynamic therapy without noticeable dark toxicity, and this strategy was able to induce a remarkably improved synergistic therapeutic effect to both superficial and deep regions of tumors under mild conditions compared with either single photothermal or photodynamic mechanisms. PMID:27503666

  3. Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

    PubMed Central

    Rollakanti, Kishore R.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2014-01-01

    Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients. PMID:25599015

  4. Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies

    NASA Astrophysics Data System (ADS)

    Yan, Xuefeng; Hu, Hao; Lin, Jing; Jin, Albert J.; Niu, Gang; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

    2015-01-01

    Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT.

  5. Evaluation of the Photodynamic Therapy effect using a tumor model in Chorioallantoic Membrane with Melanoma cells

    NASA Astrophysics Data System (ADS)

    Buzzá, Hilde H.; Pires, Layla; Bagnato, Vanderlei S.; Kurachi, Cristina

    2014-03-01

    Photodynamic Therapy (PDT) is a type of cancer treatment that is based on the interaction of light (with specific wavelength), a photosensitizing agent and molecular oxygen. The photosensitizer (PS) is activated by light and reacts with oxygen resulting in the production of singlet oxygen that is highly reactive and responsible for the cell death. The Chick Chorioallantoic Membrane (CAM) model is a transparent membrane that allows visualization and evaluation of blood vessels and structural changes, where a tumor model was developed. Two induction tumor models were investigated: tumor biopsy or cell culture. It was used a murine melanoma cell B16F10 in culture and a biopsy from a xenograft tumor in hairless mouse. Two PS were tested: Photodithazine® and Photogem®, a chlorine and porphyrin compounds, respectively. Using intravenous administration, the light-drug interval was of 30 minutes, 1 and 3 hours. Illumination was performed at 630 nm and 660 nm, and the vascular and tumor response was monitored and analyzed. The PS distribution was checked with confocal microscopy. This model can be useful to study several parameters of PDT and the effect of this therapy in the cancer treatment since it allows direct visualization of its effects.

  6. Selenorhodamine Photosensitizers for Photodynamic Therapy of P-Glycoprotein-Expressing Cancer Cells

    PubMed Central

    2015-01-01

    We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin. PMID:25250825

  7. Effect of GFP expression on the sensitivity of glioma cell lines to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Khatami, S.; Rendon, A.; Yoshimitsu, M.; Medin, J.; Lilge, L.

    2005-09-01

    Enhanced green fluorescent protein (EGFP)-expressing cells are customarily used in a variety of in vitro and in vivo studies and assays to ease visualization and localization. Nonetheless, the effects of EGFP expression on cellular responsivity to Photodynamic therapy (PDT), a combination therapy combining a photoactive drug and light, have yet to be characterized. To address this effect, rat astrocytoma cells (CNS-1), a lentivirus-transduced EGFP variant (CNS-1 GFP), human glioblastoma (U-87), and the transfected EGFP variant (U-87 GFP) are analyzed in terms of cell survival following PDT mediated by two different photoactive drugs. Cell survival is quantified via colony forming assays and Alamar blue assays, as a function of light dose, using the photosensitizers Photofrin (1ug ml-1 for 24h) and ALA (200ug ml-1 for 5h). Furthermore, effect of GFP expression on the responsivity to Cisplatin, a DNA-binding chemotherapeutic agent is determined for these cell lines. Our results show that EGFP expression does not affect the responsivity of Photofrin-PDT in comparison to parental cell lines (non GFP expressing cells), but does alter that of ALA-PDT. No change in responsivity is observed for Cisplatin treatment for either cell line. These results can be explained by oxidative stress induced by EGFP expression. This work will establish under which circumstances it is appropriate to use EGFP-expressing cell lines in the context of PDT preclinical research in vivo and in vitro.

  8. Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

    PubMed

    Nair, Lakshmi V; Nazeer, Shaiju S; Jayasree, Ramapurath S; Ajayaghosh, Ayyappanpillai

    2015-06-23

    Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 μg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC. PMID:25970038

  9. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  10. Magnetic resonance image-guided photodynamic therapy of xenograft pancreas tumors with verteporfin

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2009-02-01

    Pancreatic cancer generally has very poor prognosis, with less than 4% survival at 5 years after diagnosis. This dismal survival rate is in part due to the aggressive nature of the adenocarcinoma, leading to a late-stage at diagnosis and exhibits resistance to most therapies. Photodynamic therapy (PDT) is a model cellular and vascular therapy agent, which uses light activation of the delivered drug to photosensitize the local cellular millieu. We suggest that interstitial verteporfin (benzoporphyrin derivative monoacid ring A) PDT has the potential to be an adjuvant therapy to the commonly used Gemcitabine chemotherapy. In the current study, an orthotopic pancreatic cancer model (Panc-1) has undergone interstitial verteporfin PDT (40 J/cm with verteporfin and 40 J/cm without verteporfin). Prior to PDT, magnetic resonance (MR) imaging was used to determine the location and size of the tumor within the pancreas, allowing accurate placement of the diffusing fiber. The success of therapy was monitored in vivo by assessing the total tumor and vascular perfusion volumes 24 hours pre- and 48 hours post-PDT. Total tumor and vascular perfusion volumes were determined using T2 weighted (T2W) and Gd-DTPA difference T1 weighted (T1W) turbo spin echo (TSE) MR imaging sequences, respectively. The validity of the in vivo imaging for therapeutic response was confirmed by ex vivo fluorescence and histological staining of frozen tissue sections. The ex vivo DiOC7(3) fluorescence analysis correlates well with the information provided from the MR images, indicating that MR imaging will be a successful surrogate marker for interstitial PDT.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Targeted Iron-Oxide Nanoparticle for Photodynamic Therapy and Imaging of Head and Neck Cancer

    PubMed Central

    2015-01-01

    Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic. PMID:24923902

  10. 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.

  11. 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

  12. Lifetime-resolved photoacoustic (LPA) spectroscopy for monitoring oxygen change and photodynamic therapy (PDT)

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding

    2016-03-01

    The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.

  13. Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer

    PubMed Central

    Lucena, Silvia Rocío; Salazar, Nerea; Gracia-Cazaña, Tamara; Zamarrón, Alicia; González, Salvador; Juarranz, Ángeles; Gilaberte, Yolanda

    2015-01-01

    Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer. PMID:26516853

  14. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

    PubMed

    Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

    2015-02-01

    Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy. PMID:25483028

  15. Redox-Responsive Porphyrin-Based Polysilsesquioxane Nanoparticles for Photodynamic Therapy of Cancer Cells

    PubMed Central

    Vega, Daniel L.; Lodge, Patrick; Vivero-Escoto, Juan L.

    2015-01-01

    The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs) built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl) porphyrin (TCPP) silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS)/ζ-potential, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material. PMID:26729110

  16. The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit

    PubMed Central

    Lee, Young-Ho; Park, Ho-Won; Lee, Ju-Hyun; Seo, Hyun-Woo; Lee, Si-Young

    2012-01-01

    The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain–heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose. PMID:23222991

  17. Apoptotic and autophagic responses to photodynamic therapy in 1c1c7 murine hepatoma cells

    PubMed Central

    Andrzejak, Michelle; Price, Michael

    2011-01-01

    Photodynamic therapy (PDT) is a process that can induce apoptosis, autophagy or both depending on the cell phenotype. Apoptosis is a pathway to cell death while autophagy can protect from photokilling or act as a death pathway. In a previous study, we reported a cytoprotective effect of autophagy in murine leukemia cell lines where both autophagy and apoptosis occur within minutes after irradiation of photosensitized cells. In this study, we examined the effects of mitochondrial photodamage catalyzed by low (≤1 µM) concentrations of the photosensitizing agent termed benzoporphyrin derivative (BPD, Verteporfin) on murine hepatoma 1c1c7 cells. Apoptosis was not observed until several hours after irradiation of photosensitized cells. Autophagy was clearly cytoprotective since PDT efficacy was significantly enhanced in a knockdown sub-line (KD) in which the level of a critical autophagy protein (Atg7) was markedly reduced. This result indicates that autophagy can protect from phototoxicity even when apoptosis is substantially delayed. Much higher concentrations (≥10 µM) of BPD had previously been shown to inhibit autophagosome formation. Phototoxicity studies performed with 10 µM BPD and a proportionally reduced light dose were consistent with the absence of an autophagic process in wild-type (WT) cells under these conditions. PMID:21555918

  18. Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

    PubMed

    Yan, Xuefeng; Niu, Gang; Lin, Jing; Jin, Albert J; Hu, Hao; Tang, Yuxia; Zhang, Yujie; Wu, Aiguo; Lu, Jie; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

    2015-02-01

    Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by π-π stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT. The fluorescence of loaded DVDMS is drastically enhanced via intramolecular charge transfer. Meanwhile, the GO-PEG vehicles can significantly increase the tumor accumulation efficiency of DVDMS and lead to an improved PDT efficacy as compared to DVDMS alone. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. Most intriguingly, 100% in vivo tumor elimination was achieved by intravenous injection of GO-PEG-DVDMS (2 mg/kg of DVDMS, 50 J) without tumor recurrence, loss of body weight or other noticeable toxicity. This novel GO-PEG-DVDMS theranostics is well suited for enhanced fluorescence imaging guided PDT. PMID:25542797

  19. Assessment of Rose Bengal vs. Riboflavin Photodynamic Therapy for Inhibition of Fungal Keratitis Isolates

    PubMed Central

    Arboleda, Alejandro; Miller, Darlene; Cabot, Florence; Taneja, Mukesh; Aguilar, Mariela C.; Alawa, Karam; Amescua, Guillermo; Yoo, Sonia H.; Parel, Jean-Marie

    2014-01-01

    Purpose To compare the in vitro effect of rose bengal and riboflavin as photosensitizing agents for photodynamic therapy (PDT) on fungal isolates that are common causes of fungal keratitis Design Experimental study Methods Three isolates (Fusarium solani, Aspergillus fumigatus, Candida albicans) recovered from patients with confirmed fungal keratitis were used in the experiments. Isolates were grown on Sabouraud-Dextrose agar, swabbed and prepared in suspension, and one milliliter aliquots were inoculated onto test plates in triplicate. Test plates were separated into 5 groups: Group 1 - no treatment, Group 2 - 0.1% rose bengal alone, Group 3 - 518 nm irradiation alone, Group 4 - riboflavin PDT (riboflavin + 375 nm irradiation), and Group 5 - rose bengal PDT (rose bengal + 518 nm irradiation). Irradiation was performed over a circular area using either a green LED array (peak wavelength: 518 nm) or a UV-A LED array (peak wavelength: 375 nm). Test plates were irradiated with an energy density of 5.4 J/cm2. Later, plates were placed in a 30° C incubator and observed for growth. Results Rose bengal-mediated PDT successfully inhibited the growth of all three fungal isolates in the irradiated area. All other groups exhibited unrestricted growth throughout the plate. Conclusions Rose bengal-mediated PDT successfully inhibited the growth of three types of fungi. No other experimental groups, including riboflavin-mediated PDT, had any inhibitory effect on the isolates. The results might be useful for the treatment of patients suffering from corneal infection. PMID:24792103

  20. Nanoscale Metal–Organic Framework for Highly Effective Photodynamic Therapy of Resistant Head and Neck Cancer

    PubMed Central

    2015-01-01

    Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species (e.g., 1O2). Here we report the rational design of a Hf–porphyrin nanoscale metal–organic framework, DBP–UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP–UiO efficiently generates 1O2 owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile 1O2 diffusion through porous DBP–UiO nanoplates. Consequently, DBP–UiO displayed greatly enhanced PDT efficacy both in vitro and in vivo, leading to complete tumor eradication in half of the mice receiving a single DBP–UiO dose and a single light exposure. NMOFs thus represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic. PMID:25407895

  1. Efficacy of intravenous delta-aminolaevulinic acid photodynamic therapy on rabbit papillomas.

    PubMed Central

    Lofgren, L. A.; Ronn, A. M.; Nouri, M.; Lee, C. J.; Yoo, D.; Steinberg, B. M.

    1995-01-01

    Endogenously induced protoporphyrin IX (PPIX), a metabolite of delta-aminolaevulinic acid (ALA), has been evaluated as a photosensitising agent for destruction of papillomas in cottontail rabbit papillomavirus-infected Dutch belted and New Zealand rabbits. Three factors were evaluated: (1) relative retention ratio of drug in normal tissue, papilloma and plasma over time; (2) tissue tolerance to treatment factors; and (3) efficacy of treatment protocol. Three drug doses of ALA were examined: 50, 100 and 200 mg kg-1. Actual PPIX concentrations in tissue and plasma were determined spectrophotofluorometrically. The optimal treatment time occurred 3-6 h post ALA injection. The highest PPIX concentration ratio between papilloma and normal skin was 6:1. Different light doses were investigated, using an injection to exposure interval of 3 h and an irradiance of 100 mW cm-2 at a wavelength of 630 nm. Efficacy without risk of significant damage to normal skin was obtained using 100-200 mg kg-1 ALA and 40-60 J cm-2. A long-term (3 months) cure rate of 82% was obtained with a single treatment, provided that papilloma depth did not exceed 8 mm, volume was not more than 1000 mm3 and the plasma concentration of PPIX immediately before exposure was above 500 micrograms ml-1. The short time between injection and treatment and high efficacy, together with PPIX disappearance from plasma and tissue within 24 h, make injected ALA a highly attractive drug for photodynamic therapy. PMID:7547231

  2. The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit.

    PubMed

    Lee, Young-Ho; Park, Ho-Won; Lee, Ju-Hyun; Seo, Hyun-Woo; Lee, Si-Young

    2012-12-01

    The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain-heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose. PMID:23222991

  3. Molecular Electronic Tuning of Photosensitizers to Enhance Photodynamic Therapy: Synthetic Dicyanobacteriochlorins as a Case Study

    PubMed Central

    Yang, Eunkyung; Diers, James R.; Huang, Ying-Ying; Hamblin, Michael R.; Lindsey, Jonathan S.; Bocian, David F.; Holten, Dewey

    2012-01-01

    Photophysical, photostability, electrochemical, and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ≈ BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35–50 nm (748–763 nm) from that for BC (713 nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm (1.1 eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron-transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC-Pd, has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation, and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents. PMID:23163632

  4. In vitro characterization of monoaspartyl chlorin e6 and diaspartyl chlorin e6 for photodynamic therapy.

    PubMed

    Roberts, W G; Shiau, F Y; Nelson, J S; Smith, K M; Berns, M W

    1988-05-01

    The characteristics of two new chlorin photosensitizers were studied in cell culture by determining phototoxicity, subcellular localization, and photophysical properties. Monoaspartyl chlorin e6 (MACE) and diaspartyl chlorin e6 (DACE) are new photosensitizers that show promise for use in photodynamic therapy. These chlorins are pure, monomeric compounds as determined by high-pressure liquid chromatography. Both compounds absorb substantially at a longer wavelength (664 nm) than does dihematoporphyrin ether-ester (DHE). Tumor diagnosis with the use of fluorescence should be facilitated due to the purity of the compounds and the single fluorescence emission peak. Phototoxicity dose-response curves of the sensitizers were completed using a standard clonogenic assay to determine cell viability. The chlorins showed good sensitizing capabilities with light. In addition, subcellular localization of MACE, DACE, and DHE was studied using fluorescence microscopy. Whereas DHE was located throughout the cytoplasm, the primary site of localization of the chlorins appeared to be in the lysosome. The results demonstrate that MACE and DACE are effective photosensitizing agents in vitro and compare favorably to DHE. PMID:2965763

  5. Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer

    PubMed Central

    Meyers, Joseph D.; Cheng, Yu; Agnes, Richard S.; Schluchter, Mark D.; Margevicius, Seunghee; Wang, Xinning; Kenney, Malcolm E.

    2015-01-01

    Targeted drug delivery using epidermal growth factor peptide-targeted gold nanoparticles (EGFpep-Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGFpep-Au NP-Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGFpep-Au NP-Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGFpep-Au NP-Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGFpep-Au NP-Pc 4 results in interrupted tumor growth when compared with EGFpep-Au NP control mice when selectively activated with light. These data demonstrate that EGFpep-Au NP-Pc 4 utilizes cancer-specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery. PMID:25999665

  6. In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy.

    PubMed

    Lim, Siang Hui; Thivierge, Cliferson; Nowak-Sliwinska, Patrycja; Han, Junyan; van den Bergh, Hubert; Wagnières, Georges; Burgess, Kevin; Lee, Hong Boon

    2010-04-01

    To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer. PMID:20199028

  7. 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

  8. 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

  9. 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

  10. 5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in treatment of laryngeal papilloma: Case report.

    PubMed

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao; Huang, Zheng

    2016-06-01

    This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy in the treatment of three patients with juvenile laryngeal papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus, frequent recurrence and possibility of spreading to the lower respiratory tract. ALA-PDT via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy is safe and effective for clearing laryngeal papilloma, laryngeal papilloma was fully removed from the three patients, with no recurrence during the 6-24 months of follow-up medical examination. 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser can be used for treating laryngeal papilloma. PMID:27045601

  11. Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Ding, Hui; Lv, Yanlin; Ni, Dezhi; Wang, Jie; Tian, Zhiyuan; Wei, Wei; Ma, Guanghui

    2015-05-01

    A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen (3O2) and the singlet oxygen (1O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen (3O2) and the singlet oxygen (1O2) as compared to the previously developed PDT agents with

  12. 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

  13. ``Smart'' theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Das, Gautom Kumar; Vijayaragavan, Vimalan; Xu, Qing Chi; Padmanabhan, Parasuraman; Bhakoo, Kishore K.; Tamil Selvan, Subramanian; Tan, Timothy Thatt Yang

    2014-10-01

    The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01717j

  14. Photodynamic therapy and the treatment of neoplastic diseases of the larynx

    NASA Astrophysics Data System (ADS)

    Biel, Merrill A.

    1995-05-01

    Photodynamic therapy (PDT) is an innovative treatment involving the use of light-sensitive drugs to selectively identify and destroy diseased cells. Therefore, photodynamic therapy has the potential to treat and cure precancerous and early cancerous lesions (carcinoma in situ (CIS), T1 and T2) of the larynx while preserving normal tissue. Twenty-four patients with recurrent leukoplakia and carcinomas of the larynx were treated with PDT with follow-up to 60 months. Fourteen patients with T1 squamous cell carcinomas of the vocal cord, 2 patients with a T2 squamous cell carcinoma of the vocal cord failing radiotherapy, and 6 patients with CIS and sever atypia were treated with PDT and obtained a complete response and are disease free. One patient with a T3 carcinoma of the larynx was treated with PDT but died 5 weeks post-treatment of unrelated causes and could not be assessed. Photodynamic therapy is a promising therapy for treatment of precancerous and cancerous lesions of the larynx. This therapy may be particularly beneficial for the treatment of recurrent carcinomas of the larynx that have failed conventional radiotherapy, thereby preserving voice and eliminating the need for destructive laryngeal surgery.

  15. 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

  16. 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.

  17. WS2 nanosheet as a new photosensitizer carrier for combined photodynamic and photothermal therapy of cancer cells

    NASA Astrophysics Data System (ADS)

    Yong, Yuan; Zhou, Liangjun; Gu, Zhanjun; Yan, Liang; Tian, Gan; Zheng, Xiaopeng; Liu, Xiaodong; Zhang, Xiao; Shi, Junxin; Cong, Wenshu; Yin, Wenyan; Zhao, Yuliang

    2014-08-01

    We have developed a simple and efficient strategy to fabricate WS2 nanosheets with low toxicity and good water solubility via a liquid exfoliation method by using H2SO4 intercalation and ultrasonication. The as-prepared WS2 nanosheets were employed not only as an NIR absorbing agent for photothermal therapy (PTT) but also as a photosensitizer (PS) carrier for photodynamic therapy (PDT) due to their sheet like structure that offers large surface area to load PS molecules. Moreover, singlet-oxygen generation of the PSs-WS2 complex could be finely controlled by NIR irradiation that could manipulate the PSs release behavior from WS2 nanosheets. The synergistic anti-tumor effect of WS2 nanosheets mediated PDT-PTT was also evaluated carefully and the results clearly showed that the efficacy of combined PDT-PTT treatment of cancer cells is significantly higher than those of PDT-only and PTT-only treatment, indicating enhanced efficiency of the combined therapeutic system. In addition, the WS2 could be used as a computed tomography (CT) contrast agent for bio-imaging since W atoms have strong X-ray attenuation ability, making them a multifunctional theranostic platform for simultaneous imaging-guided diagnosis and therapy.We have developed a simple and efficient strategy to fabricate WS2 nanosheets with low toxicity and good water solubility via a liquid exfoliation method by using H2SO4 intercalation and ultrasonication. The as-prepared WS2 nanosheets were employed not only as an NIR absorbing agent for photothermal therapy (PTT) but also as a photosensitizer (PS) carrier for photodynamic therapy (PDT) due to their sheet like structure that offers large surface area to load PS molecules. Moreover, singlet-oxygen generation of the PSs-WS2 complex could be finely controlled by NIR irradiation that could manipulate the PSs release behavior from WS2 nanosheets. The synergistic anti-tumor effect of WS2 nanosheets mediated PDT-PTT was also evaluated carefully and the results

  18. Pleural Photodynamic Therapy and Surgery in Lung Cancer and Thymoma Patients with Pleural Spread

    PubMed Central

    Tseng, Ying-Fan; Shieh, Ming-Jium; Chen, Jin-Shing; Lai, Hong-Shiee; Lee, Jang-Ming

    2015-01-01

    Pleural spread is difficult to treat in malignancies, especially in lung cancer and thymoma. Monotherapy with surgery fails to have a better survival benefit than palliative chemotherapy, the currently accepted treatment. Photodynamic therapy utilizes a photosensitizer to target the tumor site, and the tumor is exposed to light after performing a pleurectomy and tumor resection. However, the benefits of this procedure to lung cancer or thymoma patients are unknown. We retrospectively reviewed the clinical characteristics and treatment outcomes of patients with lung cancer or thymoma with pleural seeding who underwent pleural photodynamic therapy and surgery between 2005 and 2013. Eighteen patients enrolled in this study. The mean patient age was 52.9 ± 12.2 years. Lung cancer was the inciting cancer of pleural dissemination in 10 patients (55.6%), and thymoma in 8 (44.4%). There was no procedure-related mortality. Using Kaplan-Meier survival analysis, the 3-year survival rate and the 5-year survival rate were 68.9% and 57.4%, respectively. We compared the PDT lung cancer patients with those receiving chemotherapy or target therapy (n = 51) and found that the PDT group had better survival than non-PDT patients (mean survival time: 39.0 versus 17.6 months; P = .047). With proper patient selection, radical surgical resection combined with intrapleural photodynamic therapy for pleural spread in patients with non-small cell lung cancer or thymoma is feasible and may provide a survival benefit. PMID:26193470

  19. Three-dimensional in vitro cancer spheroid models for Photodynamic Therapy: Strengths and Opportunities

    NASA Astrophysics Data System (ADS)

    Evans, Conor

    2015-03-01

    Three dimensional, in vitro spheroid cultures offer considerable utility for the development and testing of anticancer photodynamic therapy regimens. More complex than monolayer cultures, three-dimensional spheroid systems replicate many of the important cell-cell and cell-matrix interactions that modulate treatment response in vivo. Simple enough to be grown by the thousands and small enough to be optically interrogated, spheroid cultures lend themselves to high-content and high-throughput imaging approaches. These advantages have enabled studies investigating photosensitizer uptake, spatiotemporal patterns of therapeutic response, alterations in oxygen diffusion and consumption during therapy, and the exploration of mechanisms that underlie therapeutic synergy. The use of quantitative imaging methods, in particular, has accelerated the pace of three-dimensional in vitro photodynamic therapy studies, enabling the rapid compilation of multiple treatment response parameters in a single experiment. Improvements in model cultures, the creation of new molecular probes of cell state and function, and innovations in imaging toolkits will be important for the advancement of spheroid culture systems for future photodynamic therapy studies.

  20. Can Antimicrobial Photodynamic Therapy (aPDT) Enhance the Endodontic Treatment?

    PubMed

    Chiniforush, Nasim; Pourhajibagher, Maryam; Shahabi, Sima; Kosarieh, Emad; Bahador, Abbas

    2016-01-01

    In order to achieve a long-lasting effect, one of the main goals in root canal treatment is to eliminate the endodontic bacteria. Conventional chemomechanical debridement is considered as the basic treatment in root canal therapy, but adjunctive techniques such as antimicrobial photodynamic therapy (aPDT) can also be helpful. The aim of this study was to evaluate reports in the scientific literature that used different photosensitizers (PSs) for bacterial reduction. The literature search was conducted using databases including PubMed, Scopus, and Google Scholar with the keywords "photodynamic therapy," "antimicrobial photodynamic therapy," or "photoactivated disinfection" and "endodontic," "Enterococcus faecalis," or "root canal treatment," from 2000 to 2015. By evaluating different studies, it was concluded that aPDT should be applied in combination with conventional mechanical debridement and irrigants. However, it is also important to note that the success rate is critically dependent on the type of the PS, output power of the laser used, irradiation time, pre-irradiation time, and type of tips used. PMID:27330702

  1. Proposal of thermal imaging application in photodynamic therapy-Preliminary report.

    PubMed

    Cholewka, Armand; Stanek, Agata; Kwiatek, Sebastian; Cholewka, Agnieszka; Cieślar, Grzegorz; Straszak, Dariusz; Gibińska, Joanna; Sieroń-Stołtny, Karolina

    2016-06-01

    There are many different skin lesions that manifest a skin temperature gradient. Basal cell carcinoma (BCC) is the most frequently occurring type of malignant skin lesion (almost 95% of all skin tumors). BCC is sometimes treated by using photodynamic therapy which is very well tolerated by patients and provides good results, especially in superficial skin layer lesions. The results of our studies showed significant changes in the area of temperature gradient due to photodynamic therapy. It seems that the ability to acquire knowledge of such area changes may provide additional useful information to physicians. The increase of observed isotherm area in comparison to lesion size on the skin was a few times higher. It may suggest the range of areas where the metabolism processes take place. Due to the accumulation of photosensitivity only in tumor cells, we theorize that such a large region of increased metabolism observed during therapy may be connected with a larger range of tumor cells than was previously predicted through diagnosis. However, it should be noted that the region can be much bigger due to the existing heat transfer. The results obtained have a potential meaning in describing the range of chemical and physiological processes occurring during photodynamic therapy. PMID:26687617

  2. Drug therapy reviews: antirheumatic agents.

    PubMed

    Evens, R P

    1979-05-01

    The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. PMID:377958

  3. 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

  4. 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

  5. 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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

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

  8. Spectral matching technology for light-emitting diode-based jaundice photodynamic therapy device

    NASA Astrophysics Data System (ADS)

    Gan, Ru-ting; Guo, Zhen-ning; Lin, Jie-ben

    2015-02-01

    The objective of this paper is to obtain the spectrum of light-emitting diode (LED)-based jaundice photodynamic therapy device (JPTD), the bilirubin absorption spectrum in vivo was regarded as target spectrum. According to the spectral constructing theory, a simple genetic algorithm as the spectral matching algorithm was first proposed in this study. The optimal combination ratios of LEDs were obtained, and the required LEDs number was then calculated. Meanwhile, the algorithm was compared with the existing spectral matching algorithms. The results show that this algorithm runs faster with higher efficiency, the switching time consumed is 2.06 s, and the fitting spectrum is very similar to the target spectrum with 98.15% matching degree. Thus, blue LED-based JPTD can replace traditional blue fluorescent tube, the spectral matching technology that has been put forward can be applied to the light source spectral matching for jaundice photodynamic therapy and other medical phototherapy.

  9. Curative effect of photodynamic therapy of pulse laser on cancer detected by computer

    NASA Astrophysics Data System (ADS)

    Sun, Xiuzhen

    1993-03-01

    The computer diagnosis apparatus for human diseases is used to detect the curative effect of photodynamic therapy (PDT). It directly takes the electric signals from auricular acupuncture points of patients turns the signals into data and displays the data on the screen. Comparing the data with the critical point, it gives out the diagnosis of the condition of the disease. If the signals are detected many times in the period of the photodynamic therapy, the change of the condition and the effect will be perceived. This provides scientific data for doctors' clinical diagnoses. The apparatus, combining computer and laser technology with Chinese traditional auricular diagnosis, has many advantages: quickness, preciseness, no injury, no pain, and no side effect. It can also store and print out cases. It's an ideal detector in the field of auricular acupuncture point diagnosis.

  10. Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro.

    PubMed

    Yang, Xiaoke; Fei, Jinbo; Li, Qi; Li, Junbai

    2016-05-01

    Monodispersed diphenylalanine-based nanospheres with excellent biocompatibility are fabricated through a facile covalent reaction-induced assembly. Interestingly, the nanospheres exhibit red autofluorescence. Most importantly, such assembled dipeptide nanospheres can serve as intrinsic photosensitizer to convert O2 to singlet oxygen ((1) O2 ). Thus, photodynamic therapy in vitro can be achieved effectively. The versatile strategy could be extended to other biomolecules containing a primary amine group for the fabrication of potential intrinsic photosensitizers. PMID:26934079

  11. Curative effect of photodynamic therapy for 42 cases of moderate or late stage in esophagus cancer

    NASA Astrophysics Data System (ADS)

    Bai, Xiao-Min; Shen, Guang-Rong; Chen, Weng-Ge; Guo, Tao

    1998-11-01

    34 patients with advanced esophagus cancer and 8 cases of cancer of gastric cardia were treated by photodynamic therapy. The therapeutic effectiveness of the treatment was evaluated according the criteria used in China. CR 63.2 percent SR 11.3 percent, MR 2 percent. The total effective rate was 76.5 percent. There was no significant side effect in this group except mild skin photosensitization and pigmentation and exacerbation of pain in a few cases.

  12. Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy.

    PubMed

    Chen, Zhuo; Xu, Peng; Chen, Jincan; Chen, Hongwei; Hu, Ping; Chen, Xueyuan; Lin, Lin; Huang, Yunmei; Zheng, Ke; Zhou, Shanyong; Li, Rui; Chen, Song; Liu, Jianyong; Xue, Jinping; Huang, Mingdong

    2014-10-01

    Photodynamic therapy (PDT) has attracted much interest for the treatment of cancer due to the increased incidence of multidrug resistance and systemic toxicity in conventional chemotherapy. Phthalocyanine (Pc) is one of main classes of photosensitizers for PDT and possesses optimal photophysical and photochemical properties. A higher specificity can ideally be achieved when Pcs are targeted towards tumor-specific receptors, which may also facilitate specific drug delivery. Herein, we develop a simple and unique strategy to prepare a hydrophilic tumor-targeting photosensitizer ATF-ZnPc by covalently coupling zinc phthalocyanine (ZnPc) to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA), a fragment responsible for uPA receptor (uPAR, a biomarker overexpressed in cancer cells), through the carboxyl groups of ATF. We demonstrate the high efficacy of this tumor-targeting PDT agent for the inhibition of tumor growth both in vitro and in vivo. Our in vivo optical imaging results using H22 tumor-bearing mice show clearly the selective accumulation of ATF-ZnPc in tumor region, thereby revealing the great potential of ATF-ZnPc for clinical applications such as cancer detection and guidance of tumor resection in addition to photodynamic treatment. PMID:24969665

  13. Synthesis and characterization of photo-functional magnetic nanoparticles (Fe3O4@HP) for applications in photodynamic cancer therapy

    NASA Astrophysics Data System (ADS)

    Choi, Kyong-Hoon; Nam, Ki Chang; Kim, Ho-Joong; Min, Jeeeun; Uhm, Han Sup; Choi, Eun Ha; Park, Bong Joo; Jung, Jin-Seung

    2014-11-01

    Nowadays, photodynamic therapy (PDT) is a quite promising approach for killing various cancer cells. In this work, we report on photo-functional magnetic nanoparticles conjugated with hematoporphyrin (HP) (Fe3O4@HP) via a simple surface modification process. The microstructure and the magnetic properties of the Fe3O4 nanoparticles were investigated by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and vibrating sample magnetometry (VSM), and the biocompatibility and the photo-killing activity were evaluated using mammalian cells in vitro to confirm the potential of these particles for use as an agent for PDT application. We have demonstrated that the Fe3O4@HP nanoparticles show good biocompatibilities in fibroblast (L-929) and prostate cancer (PC-3) cells and have remarkable photodynamic anticancer activities. Especially, the photo-killing activities for 25, 50, and 100 μg/ml of Fe3O4@HP were found to be above 86% (86.6, 99.2, and 99.4%, respectively) in PC-3 cells, demonstrating significantly high anticancer effects on prostate cancer cells, these effects depend on the concentration of the Fe3O4@HP nanoparticles. These results indicate that our Fe3O4@HP nanoparticles can be useful for PDT, although further studies to evaluate the cell-death mechanisms in vitro and in vivo will be needed to verify the potential for clinical PDT applications.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  15. pH-Triggered Polypeptides Nanoparticles for Efficient BODIPY Imaging-Guided Near Infrared Photodynamic Therapy.

    PubMed

    Liu, Le; Fu, Liyi; Jing, Titao; Ruan, Zheng; Yan, Lifeng

    2016-04-13

    An efficient pH-responsive multifunctional polypeptide micelle for simultaneous imaging and in vitro photodynamic therapy (PDT) has been prepared. The goal here is to detect and treat cancer cells by near-infrared fluorescence (NIRF) imaging and PDT synchronously. A photosensitizer BODIPY-Br2 with efficient singlet oxygen generation was synthesized at first which owns both seductive abilities in fluorescence emission and reactive oxygen species (ROS) generation under light irradiation. Then, amphiphilic copolymer micelles pH-triggered disassembly were synthesized from N-carboxyanhydride (NCA) monomer via a ring-opening polymerization and click reaction for the loading of BODIPY-Br2 by hydrophobic interaction, and the driving force is the protonation of the diisopropylethylamine groups conjugated to the polypeptide side chains. In vitro tests performed on HepG2 cancer cells confirm that the cell suppression rate was improved by more than 40% in the presence of light in the presence of an extremely low energy density (12 J/cm(2)) with very low concentration of 5.4 μM photosensitizer. At the same time, the internalization of the nanoparticles by cells can also be traced by NIRF imaging, indicating that the NIR nanoparticles presented imaging guided photodynamic therapy properties. It provides the potential of using polypeptide as a biodegradable carrier for NIR image-guided photodynamic therapy. PMID:27020730

  16. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia.

    PubMed

    Kawczyk-Krupka, Aleksandra; Waśkowska, Jadwiga; Raczkowska-Siostrzonek, Agnieszka; Kościarz-Grzesiok, Anna; Kwiatek, Sebastian; Straszak, Dariusz; Latos, Wojciech; Koszowski, Rafał; Sieroń, Aleksander

    2012-06-01

    Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic. PMID:22594985

  17. Activation of photodynamic therapy in vitro with Cerenkov luminescence generated from Yttrium-90 (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

    2016-03-01

    Translation of photodynamic therapy to the clinical setting has primarily been limited to easily accessible and/or superficial diseases where traditional light delivery can be performed noninvasively. Cerenkov luminescence, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively in order to overcome this depth limitation. We report on the use of Cerenkov luminescence generated from Yttrium-90 as a means to active the photodynamic therapy process in monolayer tumor cell cultures. The current study investigates the utility of Cerenkov luminescence for activating both the clinically relevant aminolevulinic acid at 1.0 mM and also the more efficient photosensitizer TPPS2a at 1.2 µM. Cells were incubated with aminolevulinic acid for 6 hours prior to radionuclide addition, as well as additional daily treatments for three days. TPPS2a was delivered as a single treatment with an 18 hour incubation time before radionuclide addition. Experiments were completed for both C6 glioma cells and MDA-MB-231 breast tumor cells. Although aminolevulinic acid proved ineffective for generating a therapeutic effect at any activity for either cell line, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 cell line. Current results demonstrate that it may be possible to generate a therapeutic effect in vivo using Cerenkov luminescence to activate the photodynamic therapy process with clinically relevant photosensitizers.

  18. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy.

    PubMed

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24-48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  19. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

    PubMed Central

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

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

    PubMed

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

    2015-08-19

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

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

    PubMed Central

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

    2015-01-01

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

  2. Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer.

    PubMed

    Ding, Hui; Lv, Yanlin; Ni, Dezhi; Wang, Jie; Tian, Zhiyuan; Wei, Wei; Ma, Guanghui

    2015-06-01

    A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo. PMID:25962428

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

    PubMed

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

    2014-07-18

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser. PMID:24971525

  4. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

    PubMed

    Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

    2015-03-01

    Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). PMID:25546823

  5. Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

    PubMed Central

    HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

    2015-01-01

    Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  8. Targeted two-photon photodynamic therapy for the treatment of subcutaneous tumors

    NASA Astrophysics Data System (ADS)

    Spangler, Charles W.; Starkey, Jean R.; Meng, Fanqing; Gong, Aijun; Drobizhev, Mikhail; Rebane, Aleksander; Moss, B.

    2005-04-01

    Photodynamic therapy (PDT) has developed into a mature technology over the past several years, and is currently being exploited for the treatment of a variety of cancerous tumors, and more recently for age-related wet macular degeneration of the eye. However, there are still some unresolved problems with PDT that are retarding a more general acceptance in clinical settings, and thus, for the most part, the treatment of most cancerous rumors still involves some combination of invasive surgery, chemotherapy and radiation treatment, particularly subcutaneous tumors. Currently approved PDT agents are activated in the Visible portion of the spectrum below 700 nm, Laser light in this spectral region cannot penetrate the skin more than a few millimeters, and it would be more desirable if PDT could be initiated deep in the Near-infrared (NIR) in the tissue transparency window (700-1000 nm). MPA Technologies, Inc. and Rasiris, Inc. have been co-developing new porphyrin PDT designed to have greatly enhanced intrinsic two-photon cross-sections (>800 GM units) whose two-photon absorption maxima lie deep in the tissue transparency window (ca. 780-850 nm), and have solubility characteristics that would allow for direct IV injection into animal models. Classical PDT also suffers from the lengthy time necessary for accumulation at the tumor site, a relative lack of discrimination between healthy and diseased tissue, particularly at the tumor margins, and difficulty in clearing from the system in a reasonable amount of time post-PDT. We have recently discovered a new design paradigm for the delivery of our two-photon activated PDT agents by incorporating the porphyrins into a triad ensemble that includes a small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR one-photon imaging agent that allows the tracking of the triad in terms of accumulation and clearance rates. We are currently using these new two-photon PDT triads in efficacy

  9. Evaluation of hypericin-mediated photodynamic therapy in combination with angiogenesis inhibitor bevacizumab using in vivo fluorescence confocal endomicroscopy

    NASA Astrophysics Data System (ADS)

    Bhuvaneswari, Ramaswamy; Thong, Patricia S. P.; Gan, Yik-Yuen; Soo, Khee; Olivo, Malini

    2010-01-01

    Photodynamic therapy (PDT) is an alternative cancer treatment modality that offers localized treatment using a photosensitizer and light. However, tumor angiogenesis is a major concern following PDT-induced hypoxia as it promotes recurrence. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), thus preventing angiogenesis. The combination of PDT with antiangiogenic agents such as bevacizumab has shown promise in preclinical studies. We use confocal endomicroscopy to study the antiangiogenic effects of PDT in combination with bevacizumab. This technique offers in vivo surface and subsurface fluorescence imaging of tissue. Mice bearing xenograft bladder carcinoma tumors were treated with PDT, bevacizumab, or PDT and bevacizumab combination therapy. In tumor regression experiments, combination therapy treated tumors show the most regression. Confocal fluorescence endomicroscopy enables visualization of tumor blood vessels following treatment. Combination therapy treated tumors show the most posttreatment damage with reduced cross-sectional area of vessels. Immunohistochemistry and immunofluorescence studies show that VEGF expression is significantly downregulated in the tumors treated by combination therapy. Overall, combining PDT and bevacizumab is a promising cancer treatment approach. We also demonstrate that confocal endomicroscopy is useful for visualization of vasculature and evaluation of angiogenic response following therapeutic intervention.

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

    DOEpatents

    Tadir, Yona; Berns, Michael W.; Monk, Brad J.; Profeta, Glen; Tromberg, Bruce J.

    1995-10-17

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

  11. Induction of Endogenous Reactive Oxygen Species in Mitochondria by Fullerene-Based Photodynamic Therapy.

    PubMed

    Li, Qian; Liu, Chenguang; Li, Hongguang

    2016-06-01

    The production of ROS in mitochondria plays critical role in photodynamic therapy (PDT). The aim of this study was to investigate whether fullerene-based PDT can induce generation of additional endogenous ROS in mitochondria. Chitosan oligosaccharide grafted fullerene conjugate (CS-C60) was synthesized as a model water-soluble fullerene. The relationship among photodynamic cytotoxicity, intracellular ROS and CS-C60 amount demonstrated that low dose fullerene could induce generation of endogenous ROS in human malignant melanoma (A375) cells. Laser scanning microscope (LSM) image shows that considerable amount of endogenous ROS was generated in mitochondria even CS-C60 could not localize into mitochondria. Assay with rotenone shows that PDT-induced endogenous ROS was generated via electron transport chain (ETC). PMID:27427601

  12. Intracellular Dual Fluorescent Lightup Bioprobes for Image-Guided Photodynamic Cancer Therapy.

    PubMed

    Han, Haijie; Jin, Qiao; Wang, Haibo; Teng, Wenzhuo; Wu, Jina; Tong, Hongxin; Chen, Tingting; Ji, Jian

    2016-07-01

    An intracellular dual fluorescent light-up bioprobe with aggregation-induced emission features and endogenously producing photosensitizer protoporphyrin IX (PpIX) abilities is designed and synthesized. The bioprobe is nonemissive in physiological environment. However, the bioprobe can selectively light up cancer cells with blue fluorescence of tetraphenylene (TPE) and red fluorescence of PpIX, owing to the release of TPE and methyl aminolevulinate after targeted internalization by cancer cells. Moreover, upon endogenous generation and accumulation of PpIX in cancer cells, efficient photodynamic ablation of cancer cells after light irradiation is demonstrated with easy regulation for optimal therapeutic efficacy. The design of such dual fluorescent light-up bioprobes might provide a new opportunity for targeted and image-guided photodynamic cancer therapy. PMID:27322139

  13. Direct imaging of singlet oxygen luminescence generated in blood vessels during photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Lin, Lisheng; Lin, Huiyun; Chen, Defu; Chen, Longchao; Wang, Min; Xie, Shusen; Gu, Ying; Wilson, Brian C.; Li, Buhong

    2014-05-01

    Singlet oxygen (1O2) is commonly recognized to be a major phototoxic component for inducing the biological damage during photodynamic therapy (PDT). In this study, a novel configuration of a thermoelectrically-cooled near-infrared sensitive InGaAs camera was developed for imaging of photodynamically-generated 1O2 luminescence. The validation of 1O2 luminescence images for solution samples was performed with the model photosensitizer Rose Bengal (RB). Images of 1O2 luminescence generated in blood vessels in vivo in a well-controlled dorsal skinfold window chamber model were also recorded during PDT. This study demonstrated the capacity of the newly-developed imaging system for imaging of 1O2 luminescence, and the first reported images of 1O2 luminescence in blood vessels in vivo. This system has potential for elucidating the mechanisms of vascular targeted PDT.

  14. Targets and Mechanisms of Photodynamic Therapy in Lung Cancer Cells: A Brief Overview

    PubMed Central

    Chiaviello, Angela; Postiglione, Ilaria; Palumbo, Giuseppe

    2011-01-01

    Lung cancer remains one of the most common cancer-related causes of death. This type of cancer typically develops over a period of many years, and if detected at an early enough stage can be eliminated by a variety of treatments including photodynamic therapy (PDT). A critical discussion on the clinical applications of PDT in lung cancer is well outside the scope of the present report, which, in turn focuses on mechanistic and other aspects of the photodynamic action at a molecular and cellular level. The knowledge of these issues at pre-clinical levels is necessary to develop, check and adopt appropriate clinical protocols in the future. This report, besides providing general information, includes a brief overview of present experimental PDT and provides some non-exhaustive information on current strategies aimed at further improving the efficacy, especially in regard to lung cancer cells. PMID:24212652

  15. Photophysical and photochemical properties of α-(8-quinolinoxy) zinc phthalocyanine for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Lv, Yuehui; Yu, Songlin; Lin, Huiyun; Li, Buhong; Xue, Jinping; Xie, Shusen

    2009-02-01

    The photophysical and photochemical properties of a newly developed photosensitizer α-(8-quinolinoxy) zinc phthalocyanine (α-(8-QLO)PcZn) were investigated for application in photodynamic therapy (PDT). The maximal Q band for α-(8-QLO)PcZn in dimethylformamide around 675 nm with the molar extinction coefficient of about 1.89×105 mol-1cm-1. The fluorescence quantum and singlet oxygen (1O2) yields were determined to be 0.18+/-0.02 and 0.62+/-0.03, respectively. α-(8-QLO) PcZn has a diffuse cytoplasmic distribution in nasopharyngeal carcinoma C666-1 cells, and the efficient photodynamic cytotoxicity was observed. Our findings of this study suggest that α-(8-QLO)PcZn is a promising second-generation photosensitizer for PDT.

  16. Examples of adjuvant treatment enhancing the antitumor effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai; Chaplin, David J.

    1999-07-01

    Strategies for improving the clinical efficacy of photodynamic therapy (PDT) in treatment of solid cancers include applications of different types of adjuvant treatments in addition to this modality that may result in superior therapeutic outcome. Examples of such an approach investigated using mouse tumor models are presented in this report. It is shown that the cures of PDT treated subcutaneous tumors can be substantially improved by adjuvant therapy with: metoclopramide (enhancement of cancer cell apoptosis), combretastatin A-4 (selective destruction of tumor neovasculature), Roussin's Black Salt (light activated tumor localized release of nitric oxide), or dendritic cell-based adoptive immunotherapy (immune rejection of treated tumor).

  17. Photodynamic therapy in a teenage girl with xeroderma pigmentosum type C.

    PubMed

    Larson, David M; Cunningham, Bari B

    2012-01-01

    Despite aggressive sun protection, most individuals with xeroderma pigmentosum (XP) develop cutaneous neoplasia, including actinic keratoses. We describe the case of a 16-year-old girl with XP type C treated safely with photodynamic therapy (PDT). Although there is little if any evidence in the literature supporting the use of aminolevulinic acid PDT in individuals with XP, they may be the ideal candidates for PDT treatment because the profound post-treatment photosensitivity and strict post-therapy sun avoidance necessitated by PDT treatment is already part of the everyday lifestyle of people with XP. PMID:22277026

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

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

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

  19. Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer.

    PubMed

    Jeong, Keunsoo; Park, Solji; Lee, Yong-Deok; Kang, Chi Soo; Kim, Hyun Jun; Park, Hyeonjong; Kwon, Ick Chan; Kim, Jungahn; Park, Chong Rae; Kim, Sehoon

    2016-08-01

    Current approaches in use of water-insoluble photosensitizers for photodynamic therapy (PDT) of cancer often demand a nano-delivery system. Here, we report a photosensitizer-loaded biocompatible nano-delivery formulation (PPaN-20) whose size was engineered to ca. 20nm to offer improved cell/tissue penetration and efficient generation of cytotoxic singlet oxygen. PPaN-20 was fabricated through the physical assembly of all biocompatible constituents: pyropheophorbide-a (PPa, water-insoluble photosensitizer), polycaprolactone (PCL, hydrophobic/biodegradable polymer), and Pluronic F-68 (clinically approved polymeric surfactant). Repeated microemulsification/evaporation method resulted in a fine colloidal dispersion of PPaN-20 in water, where the particulate PCL matrix containing well-dispersed PPa molecules inside was stabilized by the Pluronic corona. Compared to a control sample of large-sized nanoparticles (PPaN-200) prepared by a conventional solvent displacement method, PPaN-20 revealed optimal singlet oxygen generation and efficient cellular uptake by virtue of the suitably engineered size and constitution, leading to high in vitro phototoxicity against cancer cells. Upon administration to tumor-bearing mice by peritumoral route, PPaN-20 showed efficient tumor accumulation by the enhanced cell/tissue penetration evidenced by in vivo near-infrared fluorescence imaging. The in vivo PDT treatment with peritumorally administrated PPaN-20 showed significantly enhanced suppression of tumor growth compared to the control group, demonstrating great potential as a biocompatible photosensitizing agent for locoregional PDT treatment of cancer. PMID:27107384

  20. Porphyrin-based polysilsesquioxane nanoparticles to improve photodynamic therapy for cancer treatment

    NASA Astrophysics Data System (ADS)

    Vivero-Escoto, Juan L.; DeCillis, Daniel; Fritts, Laura; Vega, Daniel L.

    2014-03-01

    Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of intense scientific research. Traditionally, PS molecules (e.g. porphyrins) have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption and reduced selectivity for targeted tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles are crosslinked homopolymers formed by the condensation of functionalized trialkoxysilanes or bis(trialkoxysilanes). We believe that PSilQ particles provide an interesting platform for developing PS nanocarriers. Several advantages can be foreseen by using this platform such as carrying a large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by cells. In this work, PSilQ nanoparticles with a high payload of photosensitizers were synthesized, characterized, and applied in vitro. The network of this nanomaterial is formed by protoporphyrin IX (PpIX) molecules chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The phototoxicity of this porphyrin-based PSilQ nanomaterial was successfully demonstrated in vitro using human cervical (HeLa) cancer cells. We envision that this platform can be further functionalized with polyethylene glycol (PEG) and targeting ligands to improve its biocompatibility and target specificity.

  1. An upconversion nanoplatform for simultaneous photodynamic therapy and Pt chemotherapy to combat cisplatin resistance.

    PubMed

    Ai, Fujin; Sun, Tianying; Xu, Zoufeng; Wang, Zhigang; Kong, Wei; To, Man Wai; Wang, Feng; Zhu, Guangyu

    2016-08-16

    Platinum-based antineoplastic drugs are among the first-line chemotherapeutic agents against a variety of solid tumors, but toxic side-effects and drug resistance issues limit their clinical optimization. Novel strategies and platforms to conquer cisplatin resistance are highly desired. Herein, we assembled a multimodal nanoplatform utilizing 808 nm-excited and biocompatible core-shell-shell upconversion nanoparticles (UCNPs) [NaGdF4:Yb/Nd@NaGdF4:Yb/Er@NaGdF4] that were covalently loaded with not only photosensitizers (PSs), but also Pt(iv) prodrugs, which were rose bengal (RB) and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2NH2)2], respectively. The UCNPs had the capability to convert near infrared (NIR) light to visible light, which was further utilized by RB to generate singlet oxygen. At the same time, the nanoplatform delivered the Pt(iv) prodrug into cancer cells. Thus, this upconversion nanoplatform was able to carry out combined and simultaneous photodynamic therapy (PDT) and Pt chemotherapy. The nanoplatform was well characterized and the energy transfer efficiency was confirmed. Compared with free cisplatin or UCNPs loaded with RB only, our nanoplatform showed significantly improved cytotoxicity upon 808 nm irradiation in both cisplatin-sensitive and -resistant human ovarian cancer cells. A mechanistic study showed that the nanoparticles efficiently delivered the Pt(iv) prodrug into cancer cells, resulting in Pt-DNA damage, and that the nanoplatform generated cellular singlet oxygen to kill cancer cells. We, therefore, provide a comprehensive strategy to use UCNPs for combined Pt chemotherapy and PDT against cisplatin resistance, and our nanoplatform can also be used as a theranostic tool due to its NIR bioimaging capacity. PMID:27430044

  2. Photodynamic therapy in interplay with fluorescence diagnostics in the treatment of human superficial malignancies

    NASA Astrophysics Data System (ADS)

    Andersson, Torsten; Berg, Roger; Johansson, Jonas; Killander, Dick; Svanberg, Katarina; Svanberg, Sune; Yang, Yuanlong

    1992-06-01

    In the present paper we address the question if fluorescence diagnostics can be used to monitor and possibly predict the outcome of photodynamic therapy (PDT) using the tumor seeking agents Photofrin and (delta) -aminolevulinic acid (ALA). The degree of selective uptake may vary from patient to patient and it would be interesting to use the drug-related fluorescence signal as a tool to tailor the treatment strategy. Clearly, the fluorescence intensity cannot be directly related to the tissue drug contents because of varying absorption and scattering properties of the tissue. However, because of the real-time capability of fluorescence it is interesting to see how far the fluorescence information can be utilized for optimizing the light delivery. Patients with basal cell carcinoma and spread metastatic breast cancer in the skin were treated. Two different doses, 1 and 2 mg/kg b.w. of Photofrin (Quadra Logic, Vancouver, Canada) were used. The treatment laser was a Nd:YAG pumped dye laser (Multilase Dye 600, Technomed International, Paris/Bron, France). The system provides 1064 nm IR and 532 nm green light from the Nd:YAG laser as well as red light in the region 620 - 670 nm from a dye laser. The treatment procedure was preceded by fluorescence measurements for allowing comparisons between the diagnostic signals and the treatment outcome. At the end of the treatment, fluorescence was again monitored to assess the degree of bleaching manifested by the appearance of an additional red peak. Our data on the connection between fluorescence signals, delivered dose and observed treatment outcome are presented and the potential of imaging fluorescence monitoring in PDT dosimetry is discussed.

  3. Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

    NASA Astrophysics Data System (ADS)

    Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

    2005-04-01

    During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

  4. Reduction of the invasiveness of human glioma cells by ALA-mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Sun, Chung-Ho; Madsen, Steen

    2006-02-01

    Introduction: High grade gliomas are characterised by rapid and invasive growth, that cause massive tissue destruction at both the tumour- brain boarder as well as in regions remote from the tumor core. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study we evaluated the effects of ALA mediated photodynamic therapy (PDT) on the invesivness of human glioma cells migrating from implanted multicell tumor spheroids. Materials and method 3-400nm diameter tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. 24 hours following implantation there was a significant invasion of the surrounding gel by individual tumor cells to an average distance of 400nm. The cultures were incubated in increasing concentrations of ALA (10-1000 ug/ml) for four hours and then exposed to 635nm laser light in a titration of both fluence level and fluence rate. Results Fluences of 25J/cm2 were clearly cytotoxic for both the infiltrating cells as well as the spheroids at all ALA concentrations. Fluence levels of 6J did not stop the spheroid growth or prove cytotoxic to the glioma cells that had previously migrated into the gel, in a majority of cultures but inhibited further migration of the cells by 80-90% compared to control. Conclusion: Measurement of cell survival and cell proliferation indices seemed to indicate a direct migratory inhibition effect on the invading cells and not cytotoxicity as the most likely mechanism for this observation.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Gold nanorod@silica-carbon dots as multifunctional phototheranostics for fluorescence and photoacoustic imaging-guided synergistic photodynamic/photothermal therapy.

    PubMed

    Jia, Qingyan; Ge, Jiechao; Liu, Weimin; Liu, Sha; Niu, Guangle; Guo, Liang; Zhang, Hongyan; Wang, Pengfei

    2016-07-14

    Phototheranostics, which is the application of light in the diagnostic imaging and therapy of cancer, has shown great promise for multimodal cancer imaging and effective therapy. Herein, we developed multifunctional gold nanorod@silica-carbon dots (GNR@SiO2-CDs) as a phototheranostic agent by incorporating carbon dots (CDs) with gold nanorods (GNRs), using SiO2 as a scaffold. In GNR@SiO2-CDs, the GNRs act as both photoacoustic (PA) imaging and photothermal therapy (PTT) agents, and the CDs serve as fluorescence (FL) imaging and photodynamic therapy (PDT) agents. The introduction of SiO2 not only improves the chemical stability of the GNRs and CDs in the physiological environment but also prevents the absolute quenching of the fluorescence of the CDs by GNRs. These collective properties make GNR@SiO2-CDs a novel phototheranostic agent, in which high sensitivity and good spatial resolution of FL/PA imaging can be achieved to guide PDT/PTT treatments through i.v. administration. The combination of PDT and PTT proved to be more efficient in killing cancer cells compared to PDT or PTT alone under a low dose of laser irradiation (≤0.5 W cm(-2)). Furthermore, GNR@SiO2-CDs could be cleared out from the body of mice, indicating the low toxicity of this phototheranostic agent. Our work highlights the potential of using GNRs and CDs as novel phototheranostic agents for multifunctional cancer therapies. PMID:27326673

  11. 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

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  14. The effects of photodynamic laser therapy in the treatment of marginal chronic periodontitis

    NASA Astrophysics Data System (ADS)

    Chifor, Radu; Badea, Iulia; Avram, Ramona; Chifor, Ioana; Badea, Mîndra Eugenia

    2016-03-01

    The aim of this study was to assess the effects of the antimicrobial photodynamic laser therapy performed during the treatment of deep periodontal disease by using 40 MHz high frequency ultrasonography. The periodontal data recorded during the clinical examination before each treatment session were compared with volumetric changes of the gingiva measured on periodontal ultrasound images. The results show a significant decrease of gingival tissue inflammation proved both by a significant decrease of bleeding on probing as well as by a decrease of the gingival tissues volume on sites where the laser therapy was performed. Periodontal tissues that benefit of laser therapy besides classical non-surgical treatment showed a significant clinical improvement of periodontal status. Based on these findings we were able to conclude that the antimicrobial photodynamic laser therapy applied on marginal periodontium has important anti-inflamatory effect. The periodontal ultrasonography is a method which can provide useful data for assessing the volume changes of gingival tissues, allowing a precise monitoring of marginal periodontitis.

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

    NASA Astrophysics Data System (ADS)

    Menyaev, Yulian A.; Zharov, Vladimir P.

    2006-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  17. Enhanced photodynamic therapy and effective elimination of cancer stem cells using surfactant-polymer nanoparticles.

    PubMed

    Usacheva, Marina; Swaminathan, Suresh Kumar; Kirtane, Ameya R; Panyam, Jayanth

    2014-09-01

    Photodynamic therapy is a potentially curative treatment for various types of cancer. It involves energy transfer from an excited photosensitizer to surrounding oxygen molecules to produce cytotoxic singlet oxygen species, a process termed as type II reaction. The efficiency of photodynamic therapy is greatly reduced because of the reduced levels of oxygen, often found in tumor microenvironments that also house cancer stem cells, a subpopulation of tumor cells that are characterized by enhanced tumorigenicity and resistance to conventional therapies. We show here that encapsulation of a photosensitizer, methylene blue, in alginate-Aerosol OT nanoparticles leads to an increased production of reactive oxygen species (ROS) under both normoxic and hypoxic conditions. ROS generation was found to depend on the interaction of the cationic photosensitizer with the anionic alginate polymer. Dye-polymer interaction was characterized by formation of methylene blue dimers, potentially enabling electron transfer and a type I photochemical reaction that is less sensitive to environmental oxygen concentration. We also find that nanoparticle encapsulated methylene blue has the capacity to eliminate cancer stem cells under hypoxic conditions, an important goal of current cancer therapy. PMID:25061685

  18. Novel Methods to Incorporate Photosensitizers Into Nanocarriers for Cancer Treatment by Photodynamic Therapy

    PubMed Central

    Wang, Shouyan; Fan, Wenzhe; Kim, Gwangseong; Hah, Hoe Jin; Lee, Yong-Eun Koo; Kopelman, Raoul; Ethirajan, Manivannan; Gupta, Anurag; Goswami, Lalit N.; Pera, Paula; Morgan, Janet; Pandey, Ravindra K.

    2013-01-01

    Objective A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). Materials and Methods HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. Results HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Conclusions Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. Lasers Surg. Med. 43:686–695, 2011. PMID:22057496

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

    PubMed Central

    Cabete, Joana; Campos, Sara; Lestre, Sara

    2015-01-01

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

  20. Action of antimicrobial photodynamic therapy on heterotypic biofilm: Candida albicans and Bacillus atrophaeus.

    PubMed

    Silva, Michelle Peneluppi; Dos Santos, Thais Alves; de Barros, Patrícia Pimentel; de Camargo Ribeiro, Felipe; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2016-05-01

    The increase in survival and resistance of microorganisms organized in biofilms demonstrates the need for new studies to develop therapies able to break this barrier, such as photodynamic therapy, which is characterized as an alternative, effective, and non-invasive treatment. The objective was to evaluate in vitro the effect of antimicrobial photodynamic therapy on heterotypic biofilms of Candida albicans and Bacillus atrophaeus using rose bengal (12.5 μM) and light-emitting diode (LED) (532 nm and 16.2 J). We used standard strains of B. atrophaeus (ATCC 9372) and C. albicans (ATCC 18804). The biofilm was formed in the bottom of the plate for 48 h. For the photodynamic therapy (PDT) experimental groups, we added 100 μL of rose bengal with LED (P+L+), 100 μL of rose bengal without LED (P+L-), 100 μL of NaCl 0.9 % solution with LED (P-L+), and a control group without photosensitizer or LED (P-L-). The plates remained in agitation for 5 min (pre-irradiation) and were irradiated with LED for 3 min, and the biofilm was detached using an ultrasonic homogenizer for 30 s. Serial dilutions were plated in BHI agar and HiChrom agar and incubated at 37 °C/48 h. There was a reduction of 33.92 and 29.31 % of colony-forming units per milliliter (CFU/mL) for C. albicans and B. atrophaeus, respectively, from the control group to the group subjected to PDT. However, statistically significant differences were not observed among the P+L+, P+L-, P-L+, and P-L- groups. These results suggest that antimicrobial photodynamic therapy using rose bengal (12.5 μM) with a pre-irradiation period of 5 min and LED for 3 min was not enough to cause a significant reduction in the heterotypic biofilms of C. albicans and B. atrophaeus. PMID:26861975