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Masamitsu Tanaka, Pawel Mroz,
Tianhong Dai,
Liyi Huang,
Yuji Morimoto,
Manabu Kinoshita,
Yasuo Yoshihara,
Nariyoshi Shinomiya,
Shuhji Seki,
Koichi Nemoto,
Michael R Hamblin
[show abstract]
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ABSTRACT: We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In the present study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time non-invasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, while LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P<0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.
Photochemistry and Photobiology 01/2013; · 2.41 Impact Factor
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ABSTRACT: Photodynamic therapy (PDT) was discovered over one hundred years ago when it was observed that certain dyes could kill microorganisms when exposed to light in the presence of oxygen. Since those early days, PDT has mainly been developed as a cancer therapy and as a way to destroy proliferating blood vessels. However, recently it has become apparent that PDT may also be used as an effective antimicrobial modality and a potential treatment for localized infections. This review discusses the similarities and differences between the application of PDT for the treatment of microbial infections and for cancer lesions. Type I and type II photodynamic processes are described, and the structure-function relationships of optimal anticancer and antimicrobial photosensitizers are outlined. The different targeting strategies, intracellular photosensitizer localization, and pharmacokinetic properties of photosensitizers required for these two different PDT applications are compared and contrasted. Finally, the ability of PDT to stimulate an adaptive or innate immune response against pathogens and tumors is also covered.
Israel Journal of Chemistry 09/2012; 52(8-9):691-705. · 1.53 Impact Factor
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Masamitsu Tanaka, Pawel Mroz,
Tianhong Dai,
Liyi Huang,
Yuji Morimoto,
Manabu Kinoshita,
Yasuo Yoshihara,
Koichi Nemoto,
Nariyoshi Shinomiya,
Suhji Seki,
Michael R Hamblin
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ABSTRACT: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.
In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited.
This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.
PLoS ONE 01/2012; 7(6):e39823. · 4.09 Impact Factor
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Patrizia Agostinis PhD,
Kristian Berg PhD,
PhD Keith A. Cengel MD,
Thomas H. Foster PhD,
Albert W. Girotti PhD,
Sandra O. Gollnick PhD,
PhD Stephen M. Hahn MD,
Michael R. Hamblin PhD,
Asta Juzeniene PhD,
David Kessel PhD,
Mladen Korbelik PhD,
Johan Moan PhD, PhD Pawel Mroz MD,
PhD Dominika Nowis MD,
Jacques Piette PhD,
Brian C. Wilson PhD,
PhD Jakub Golab MD
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ABSTRACT: 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 patients with 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. CA Cancer J Clin 2011. © 2011 American Cancer Society, Inc.
CA A Cancer Journal for Clinicians 06/2011; 61(4):250 - 281. · 101.78 Impact Factor
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Patrizia Agostinis,
Kristian Berg,
Keith A Cengel,
Thomas H Foster,
Albert W Girotti,
Sandra O Gollnick,
Stephen M Hahn,
Michael R Hamblin,
Asta Juzeniene,
David Kessel,
Mladen Korbelik,
Johan Moan, Pawel Mroz,
Dominika Nowis,
Jacques Piette,
Brian C Wilson,
Jakub Golab
[show abstract]
[hide abstract]
ABSTRACT: 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 patients with 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.
CA A Cancer Journal for Clinicians 05/2011; 61(4):250-81. · 101.78 Impact Factor
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Pawel Mroz,
Yumin Xia,
Daisuke Asanuma,
Aaron Konopko,
Timur Zhiyentayev,
Ying-Ying Huang,
Sulbha K Sharma,
Tianhong Dai,
Usman J Khan,
Tim Wharton,
Michael R Hamblin
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ABSTRACT: Functionalized fullerenes represent a new class of photosensitizer (PS) that is being investigated for photodynamic therapy (PDT) of various diseases, including cancer. We tested the hypothesis that fullerenes could be used to mediate PDT of intraperitoneal (IP) carcinomatosis in a mouse model. In humans this form of cancer responds poorly to standard treatment and manifests as a thin covering of tumor nodules on intestines and on other abdominal organs. We used a colon adenocarcinoma cell line (CT26) stably expressing luciferase to allow monitoring of IP tumor burden in BALB/c mice by noninvasive real-time optical imaging using a sensitive low-light camera. IP injection of a preparation of N-methylpyrrolidinium-fullerene formulated in Cremophor-EL micelles, followed by white-light illumination delivered through the peritoneal wall (after creation of a skin flap), produced a statistically significant reduction in bioluminescence and a survival advantage in mice. FROM THE CLINICAL EDITOR: This team of investigators report on functionalized fullerenes, to be used as photosensitizer for photodynamic therapy and demonstrate the efficacy of this method in an intraperitoneal carcinomatosis mouse model.
Nanomedicine: nanotechnology, biology, and medicine 05/2011; 7(6):965-74. · 5.44 Impact Factor
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ABSTRACT: Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not advanced to a mainstream cancer treatment. Although it has been shown to be an efficient way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. This review will cover these combination approaches using immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen-associated molecular patterns, cytokines growth factors, and approaches that target regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.
Photochemical and Photobiological Sciences 05/2011; 10(5):792-801. · 2.58 Impact Factor
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ABSTRACT: Photodynamic therapy (PDT) is a promising novel therapeutic procedure for the management of a variety of solid tumors and many non-malignant diseases. PDT has been described as having a significant effect on the immune system, which may be either immunostimulatory or, in some circumstances, immunosuppressive. The immunosuppressive effects of PDT have nearly all been concerned with the suppression of the contact hypersensitivity reaction in mice. Here, we review the immunosuppressive aspects of PDT treatment and discuss some additional mechanisms that may be involved.
Photochemical and Photobiological Sciences 03/2011; 10(5):751-8. · 2.58 Impact Factor
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ABSTRACT: 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.
Expert Review of Clinical Immunology 01/2011; 7(1):75-91. · 2.07 Impact Factor
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ABSTRACT: 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.
Cancersorg (G.K. 01/2011; 3:2516-2539.
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Liyi Huang,
Ying-Ying Huang, Pawel Mroz,
George P Tegos,
Timur Zhiyentayev,
Sulbha K Sharma,
Zongshun Lu,
Thiagarajan Balasubramanian,
Michael Krayer,
Christian Ruzié,
Eunkyung Yang,
Hooi Ling Kee,
Christine Kirmaier,
James R Diers,
David F Bocian,
Dewey Holten,
Jonathan S Lindsey,
Michael R Hamblin
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ABSTRACT: Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photoactivatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e.g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a gram-positive bacterium (Staphylococcus aureus), a gram-negative bacterium (Escherichia coli), and a dimorphic fungal yeast (Candida albicans). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 microM or less) against S. aureus and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against E. coli. Only the compound with basic groups was highly active against C. albicans. Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers.
Antimicrobial Agents and Chemotherapy 09/2010; 54(9):3834-41. · 4.84 Impact Factor
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Ying-Ying Huang, Pawel Mroz,
Timur Zhiyentayev,
Sulbha K Sharma,
Thiagarajan Balasubramanian,
Christian Ruzié,
Michael Krayer,
Dazhong Fan,
K Eszter Borbas,
Eunkyung Yang,
Hooi Ling Kee,
Christine Kirmaier,
James R Diers,
David F Bocian,
Dewey Holten,
Jonathan S Lindsey,
Michael R Hamblin
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ABSTRACT: Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.
Journal of Medicinal Chemistry 05/2010; 53(10):4018-27. · 4.80 Impact Factor
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Pawel Mroz,
Ying-Ying Huang,
Angelika Szokalska,
Timur Zhiyentayev,
Sahar Janjua,
Artemissia-Phoebe Nifli,
Margaret E Sherwood,
Christian Ruzié,
K Eszter Borbas,
Dazhong Fan,
Michael Krayer,
Thiagarajan Balasubramanian,
Eunkyung Yang,
Hooi Ling Kee,
Christine Kirmaier,
James R Diers,
David F Bocian,
Dewey Holten,
Jonathan S Lindsey,
Michael R Hamblin
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ABSTRACT: Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation; 3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD(50) approximately 0.1 microM) when compared with controls such as the FDA-approved Photofrin (LD(50) approximately 10 microM) and clinically tested LuTex (LD(50) approximately 1 microM). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular-orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01).
The FASEB Journal 04/2010; 24(9):3160-70. · 5.71 Impact Factor
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ABSTRACT: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response.
We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response.
Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.
PLoS ONE 01/2010; 5(12):e15194. · 4.09 Impact Factor
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Pawel Mroz,
Jayeeta Bhaumik,
Dilek K Dogutan,
Zarmeneh Aly,
Zahra Kamal,
Laiqua Khalid,
Hooi Ling Kee,
David F Bocian,
Dewey Holten,
Jonathan S Lindsey,
Michael R Hamblin
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ABSTRACT: The in vitro photodynamic therapy activity of four imidazole-substituted metalloporphyrins has been studied using human (HeLa) and mouse (CT26) cancer cell lines: an anionic Zn porphyrin and a homologous series of three cationic Zn, Pd or InCl porphyrins. A dramatic difference in phototoxicity was found: Pd cationic>InCl cationic>Zn cationic>Zn anionic. HeLa cells were more susceptible than CT26 cells. Induction of apoptosis was demonstrated using a fluorescent caspase assay. The anionic Zn porphyrin localized in lysosomes while the cationic Zn porphyrin localized in lysosomes and mitochondria, as assessed by fluorescence microscopy. Studies using fluorescent probes suggested that the cationic Pd porphyrin produced more hydroxyl radicals as the reactive oxygen species. Thus, the cationic Pd porphyrin has high potential as a photosensitizer and gives insights into characteristics for improved molecular designs.
Cancer letters 04/2009; 282(1):63-76. · 4.86 Impact Factor
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Journal of Photochemistry and Photobiology A Chemistry 12/2008; 200(2-3):346-355. · 2.42 Impact Factor
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[show abstract]
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ABSTRACT: Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been
focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to
make them soluble and therefore able to interact with biological systems. Due to their extended π-conjugation they absorb
visible light, have a high triplet yield and can generate reactive oxygen species (ROS) upon illumination, suggesting a possible
role of fullerenes in photodynamic therapy (PDT). Depending on the functional groups introduced into the molecule, fullerenes
can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears
to involve Superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over
clinically applied photosensitizers (PSs) for mediating photodynamic therapy of certain diseases.
09/2008: pages 79-106;
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ABSTRACT: Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of nontoxic photosensitizers with harmless visible light-producing cytotoxic reactive oxygen species. PDT causes apoptosis and necrosis of tumor cells, destruction of the tumor blood supply, and activation of the immune system. The objective of this study was to compare in an animal model of metastatic cancer PDT alone and PDT combined with low-dose cyclophosphamide (CY) a treatment that has been proposed to deplete regulatory T cells (T-regs) and increase the immune response to some tumors. We used J774 tumors (a highly metastatic reticulum cell sarcoma line) and PDT with benzoporphyrin derivative monoacid ring A, verteporfin for injection (BPD; 1-mg/kg injected i.v. followed after 15 min by 150 J/cm(2) of 690-nm light). CY (50 or 150 mg/kg i.p.) was injected 48 h before light delivery. PDT alone led to tumor regressions and a survival advantage but no permanent cures were obtained. BPD-PDT in combination with low-dose CY (but not high-dose CY) led to 70% permanent cures. Low-dose CY alone gave no permanent cures but did provide a survival advantage and was shown to reduce CD4+FoxP3+ T-regs in lymph nodes, whereas high-dose CY reduced other lymphocyte classes as well. Cured animals were rechallenged with J774 cells, and the tumors were rejected in 71% of mice. Cured mice had tumor-specific T cells in spleens as determined by a (51)Cr release assay. We conclude that low-dose CY depletes T-regs and potentiates BPD-PDT, leading to tumor cures and memory immunity.
Proceedings of the National Academy of Sciences 05/2008; 105(14):5495-500. · 9.68 Impact Factor
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ABSTRACT: Cancer is a leading cause of death among modern peoples largely due to metastatic disease. The ideal cancer treatment should
target both the primary tumor and the metastases with the minimal toxicity. This is best accomplished by educating the body's
immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also
be eradicated. Photody-namic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of
the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis.
Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens,
and induction of heat-shock proteins, while the three commonest cancer therapies (surgery, chemotherapy and radiotherapy)
all tend to suppress the immune system. Like many other immunotherapies, the extent of the immune response after PDT tends
to depend on the antigenicity of the particular tumor. Combination regimens using PDT and immunostimulating treatments are
likely to emerge in the future to even further enhance immunity. These are likely to include the so called biological response
modifiers that generally consist of products obtained from pathogenic microorganisms against which mammals have evolved sophisticated
defenses involving immune activation. A series of pattern recognition molecules including toll-like receptors have been identified
that are activated by products derived from pathogens and lead to upregulation of transcription factors that induce expression
of many cytokines and inflammatory mediators, which then cause activation of macrophages, dendritic and natural killer cells.
There have been several reports of combinations of PDT with microbial derived products potentiating tumor response and leading
to long-term anti-tumor immunity. In recent years the role of regulatory T-cells in suppressing anti-tumor immunity has been
identified. Treatments such as low dose cyclophosphamide that selectively reduces T-regulatory cells can also be combined
with PDT. Methods may bedeveloped to increase the expression of particular tumor antigens before PDT. Although so far these
combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.
KeywordsPhotodynamic therapy–anti-tumor immunity–toll-like receptors–T regulatory cells–dendritic cells–cytotoxic T-cells–antigen presentation
12/2007: pages 99-113;
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[hide abstract]
ABSTRACT: Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended pi-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases.
Photochemical and Photobiological Sciences 12/2007; 6(11):1139-49. · 2.58 Impact Factor
