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Merlin JPJ, Crous A, Abrahamse H. Nano-phototherapy: Favorable prospects for cancer treatment. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1930. [PMID: 37752098 DOI: 10.1002/wnan.1930] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/01/2023] [Accepted: 09/04/2023] [Indexed: 09/28/2023]
Abstract
Nanotechnology-based phototherapies have drawn interest in the fight against cancer because of its noninvasiveness, high flexibility, and precision in terms of cancer targeting and drug delivery based on its surface properties and size. Phototherapy has made remarkable development in recent decades. Approaches to phototherapy, which utilize nanomaterials or nanotechnology have emerged to contribute to advances around nanotechnologies in medicine, particularly for cancers. A brief overviews of the development of photodynamic therapy as well as its mechanism in cancer treatment is provided. We emphasize the design of novel nanoparticles utilized in photodynamic therapy while summarizing the representative progress during the recent years. Finally, to forecast important future research in this area, we examine the viability and promise of photodynamic therapy systems based on nanoparticles in clinical anticancer treatment applications and briefly make mention of the elimination of all reactive metabolites pertaining to nano formulations inside living organisms providing insight into clinical mechanistic processes. Future developments and therapeutic prospects for photodynamic treatments are anticipated. Our viewpoints might encourage scientists to create more potent phototherapy-based cancer therapeutic modalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Affiliation(s)
- J P Jose Merlin
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Anine Crous
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
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Guo Z, Zhu AT, Fang RH, Zhang L. Recent Developments in Nanoparticle-Based Photo-Immunotherapy for Cancer Treatment. SMALL METHODS 2023; 7:e2300252. [PMID: 36960932 PMCID: PMC10192221 DOI: 10.1002/smtd.202300252] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/11/2023] [Indexed: 05/17/2023]
Abstract
Phototherapy is an emerging approach for cancer treatment that is effective at controlling the growth of primary tumors. In the presence of light irradiation, photothermal and photodynamic agents that are delivered to tumor sites can induce local hyperthermia and the production of reactive oxygen species, respectively, that directly eradicate cancer cells. Nanoparticles, characterized by their small size and tunable physiochemical properties, have been widely utilized as carriers for phototherapeutic agents to improve their biocompatibility and tumor-targeted delivery. Nanocarriers can also be used to implement various codelivery strategies for further enhancing phototherapeutic efficiency. More recently, there has been considerable interest in augmenting the immunological effects of nanoparticle-based phototherapies, which can yield durable and systemic antitumor responses. This review provides an overview of recent developments in using nanoparticle technology to achieve photo-immunotherapy.
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Affiliation(s)
- Zhongyuan Guo
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Audrey T Zhu
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Ronnie H Fang
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Liangfang Zhang
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
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Szlasa W, Janicka N, Sauer N, Michel O, Nowak B, Saczko J, Kulbacka J. Chemotherapy and Physical Therapeutics Modulate Antigens on Cancer Cells. Front Immunol 2022; 13:889950. [PMID: 35874714 PMCID: PMC9299262 DOI: 10.3389/fimmu.2022.889950] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/06/2022] [Indexed: 12/29/2022] Open
Abstract
Cancer cells possess specific properties, such as multidrug resistance or unlimited proliferation potential, due to the presence of specific proteins on their cell membranes. The release of proliferation-related proteins from the membrane can evoke a loss of adaptive ability in cancer cells and thus enhance the effects of anticancer therapy. The upregulation of cancer-specific membrane antigens results in a better outcome of immunotherapy. Moreover, cytotoxic T-cells may also become more effective when stimulated ex-vivo toward the anticancer response. Therefore, the modulation of membrane proteins may serve as an interesting attempt in anticancer therapy. The presence of membrane antigens relies on various physical factors such as temperature, exposure to radiation, or drugs. Therefore, changing the tumor microenvironment conditions may lead to cancer cells becoming sensitized to subsequent therapy. This paper focuses on the therapeutic approaches modulating membrane antigens and enzymes in anticancer therapy. It aims to analyze the possible methods for modulating the antigens, such as pharmacological treatment, electric field treatment, photodynamic reaction, treatment with magnetic field or X-ray radiation. Besides, an overview of the effects of chemotherapy and immunotherapy on the immunophenotype of cancer cells is presented. Finally, the authors review the clinical trials that involved the modulation of cell immunophenotype in anticancer therapy.
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Affiliation(s)
- Wojciech Szlasa
- Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Natalia Janicka
- Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
| | - Natalia Sauer
- Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
| | - Olga Michel
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
| | - Bernadetta Nowak
- Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Jolanta Saczko
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
| | - Julita Kulbacka
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
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Strazzi-Sahyon HB, Cintra LTA, Nakao JM, Takamiya AS, Queiroz ÍODA, Henrique Dos Santos P, de Oliveira SHP, Sivieri-Araujo G. Cytotoxicity of root canal irrigating solutions and photodynamic therapy using curcumin photosensitizer. Photodiagnosis Photodyn Ther 2022; 38:102795. [PMID: 35263668 DOI: 10.1016/j.pdpdt.2022.102795] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/20/2022] [Accepted: 03/02/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Photodynamic therapy (PDT) has shown satisfactory antibacterial effects. However, few information regarding the cytotoxicity potential of PDT using curcumin as a photosensitizer (PS) on fibroblasts are found. The aim of this in vitro study was to evaluate the cytotoxicity of root canal irrigating solutions and photodynamic therapy with curcumin PS on the L-929 cell line. METHODS Healthy mouse skin fibroblast cells were distributed into the following 7 experimental groups: G1 - culture medium DMEM (control group); G2 - 0.9% sodium chloride; G3 - 2.5% sodium hypochlorite (NaOCl); G4 - 5% NaOCl; G5 - PDT with curcumin PS at 500 mg/L + blue LED; G6 - PDT with curcumin PS at 750 mg/L + blue LED; and G7 - PDT with curcumin PS at 1000 mg/L + blue LED. All experimental groups which underwent PDT action were submitted to blue LED for 4 minutes, with a wavelength of 480 nm and energy fluency of 75 J/cm². The cultures were maintained under standard cell culture conditions (37°C, 100% humidity, 5% CO2). Cell viability analysis was performed using the colorimetric method to evaluate the periods of 6, 24, and 48 hours. Data were subjected to the Kruskal-Wallis test, followed by the Dunn test to compare groups and Friedman test to compare periods (α = 0.05). RESULTS When comparing the periods, no significant differences were observed for any of the experimental groups analyzed (p > 0.05), except for the NaOCl2.5 group that exhibited higher cell viability at 6 hours compared to the period of 48 hours (p = 0.0489). In the comparisons of the experimental groups, there were no statistically significant differences between the control group compared to all disinfection protocols, regardless of the period evaluated (p > 0.05), except for the PDT + C1000 group that showed lower cell viability (p < 0.05). CONCLUSIONS PDT with curcumin at 1000 mg/L was cytotoxic on L-929 fibroblast cell culture. However, laser-activated curcumin at a concentration of 500 mg/L presented no influence on L-929 fibroblast cell viability in in vitro conditions.
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Affiliation(s)
- Henrico Badaoui Strazzi-Sahyon
- Department of Dental Materials and Prosthodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | - Luciano Tavares Angelo Cintra
- Department of Preventive and Restorative Dentistry, Discipline of Endodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | - Jaqueline Midori Nakao
- Department of Preventive and Restorative Dentistry, Discipline of Endodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | - Aline Satie Takamiya
- Department of Surgery and Integrated Clinic, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | - Índia Olinta de Azevedo Queiroz
- Department of Preventive and Restorative Dentistry, Discipline of Endodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | - Paulo Henrique Dos Santos
- Department of Dental Materials and Prosthodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
| | | | - Gustavo Sivieri-Araujo
- Department of Preventive and Restorative Dentistry, Discipline of Endodontics, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil.
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Gunaydin G, Gedik ME, Ayan S. Photodynamic Therapy-Current Limitations and Novel Approaches. Front Chem 2021; 9:691697. [PMID: 34178948 PMCID: PMC8223074 DOI: 10.3389/fchem.2021.691697] [Citation(s) in RCA: 297] [Impact Index Per Article: 74.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 05/14/2021] [Indexed: 12/17/2022] Open
Abstract
Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900’s. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.
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Affiliation(s)
- Gurcan Gunaydin
- Department of Basic Oncology, Hacettepe University Cancer Institute, Sihhiye, Ankara, Turkey
| | - M Emre Gedik
- Department of Basic Oncology, Hacettepe University Cancer Institute, Sihhiye, Ankara, Turkey
| | - Seylan Ayan
- Department of Chemistry, Bilkent University, Ankara, Turkey
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Meng X, Deng J, Liu F, Guo T, Liu M, Dai P, Fan A, Wang Z, Zhao Y. Triggered All-Active Metal Organic Framework: Ferroptosis Machinery Contributes to the Apoptotic Photodynamic Antitumor Therapy. NANO LETTERS 2019; 19:7866-7876. [PMID: 31594301 DOI: 10.1021/acs.nanolett.9b02904] [Citation(s) in RCA: 222] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The coadministration of an iron chelator weakened the antitumor potency of the nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.
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Affiliation(s)
- Xuan Meng
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Jian Deng
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Fang Liu
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Tao Guo
- Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin 300120 , China
| | - Mengying Liu
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Peipei Dai
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Aiping Fan
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Zheng Wang
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
| | - Yanjun Zhao
- School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China
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Kawczyk-Krupka A, Czuba Z, Latos W, Wasilewska K, Verwanger T, Krammer B, Sieroń A. Influence of ALA-mediated photodynamic therapy on secretion of interleukins 6, 8 and 10 by colon cancer cells in vitro. Photodiagnosis Photodyn Ther 2018; 22:137-139. [PMID: 29510260 DOI: 10.1016/j.pdpdt.2018.02.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 01/13/2018] [Accepted: 02/26/2018] [Indexed: 10/17/2022]
Abstract
BACKGROUND Photodynamic therapy has apart from a direct cytotoxic effect also immunomodulatory properties. The aim of our study was to investigate how photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) in sublethal doses influences the secretion of interleukins 6, 8 and 10 from colon cancer cells in vitro. METHODS We used two human colon cancer cell lines SW480 and SW620 of different malignancies which were treated with a sublethal PDT protocol. Determination of interleukins was carried out using the Bio- Plex Assay Pro™ kit on the Bio- Plex Suspension Array System. RESULTS Sublethal ALA-PDT did not affect IL-6 secretion by SW480 cells, but caused a 40% decrease of IL-6 release by the SW620 cell line. It increased IL-8 secretion in both, the SW480 and SW620 cell lines, by 23% and 46%, respectively, and decreased the production of IL-10 (25% in SW480 and 32% in SW620 cells). CONCLUSIONS ALA-PDT in sublethal doses might influence colon cancer cell's progression and invasion by reducing the secretion of IL-6, IL-10 and increasing the IL-8 concentration with higher values in the more malignant cell line.
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Affiliation(s)
- Aleksandra Kawczyk-Krupka
- School of Medicine with the Division of Dentistry in Zabrze, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland.
| | - Zenon Czuba
- School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Department of Microbiology and Immunology, 19 Jordana St., 41-808 Zabrze, Poland.
| | - Wojciech Latos
- Specialist Hospital N°2, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Batorego Street 15, 41-902 Bytom, Poland.
| | - Katarzyna Wasilewska
- School of Clinical Medicine, University of Cambridge, Cambridge, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 OSP, United Kingdom
| | - Thomas Verwanger
- Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
| | - Barbara Krammer
- Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
| | - Aleksander Sieroń
- School of Medicine with the Division of Dentistry in Zabrze, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland.
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Muchowicz A, Wachowska M, Stachura J, Tonecka K, Gabrysiak M, Wołosz D, Pilch Z, Kilarski WW, Boon L, Klaus TJ, Golab J. Inhibition of lymphangiogenesis impairs antitumour effects of photodynamic therapy and checkpoint inhibitors in mice. Eur J Cancer 2017; 83:19-27. [DOI: 10.1016/j.ejca.2017.06.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 06/01/2017] [Indexed: 10/19/2022]
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Evaluation of photodynamic therapy on fibroblast viability and cytokine production. Photodiagnosis Photodyn Ther 2016; 13:97-100. [DOI: 10.1016/j.pdpdt.2016.01.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Revised: 12/19/2015] [Accepted: 01/14/2016] [Indexed: 11/18/2022]
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Anzengruber F, Avci P, de Freitas LF, Hamblin MR. T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it? Photochem Photobiol Sci 2015; 14:1492-1509. [PMID: 26062987 PMCID: PMC4547550 DOI: 10.1039/c4pp00455h] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients.
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Affiliation(s)
- Florian Anzengruber
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
- Department of Dermatology, Harvard Medical School, Boston, MA, USA
| | - Pinar Avci
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
- Department of Dermatology, Harvard Medical School, Boston, MA, USA
- Department of Dermatology, Dermatooncology and Venerology, Semmelweis University School of Medicine, Budapest, 1085, Hungary
| | - Lucas Freitas de Freitas
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
- Department of Dermatology, Harvard Medical School, Boston, MA, USA
- Programa de Pos Graduacao Interunidades Bioengenharia – USP – Sao Carlos, Brazil
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
- Department of Dermatology, Harvard Medical School, Boston, MA, USA
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA
- Correspondence to: Michael R Hamblin, PhD, Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA.
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Reinhard A, Sandborn WJ, Melhem H, Bolotine L, Chamaillard M, Peyrin-Biroulet L. Photodynamic therapy as a new treatment modality for inflammatory and infectious conditions. Expert Rev Clin Immunol 2015; 11:637-57. [DOI: 10.1586/1744666x.2015.1032256] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Basic and Clinical Aspects of Photodynamic Therapy. RESISTANCE TO TARGETED ANTI-CANCER THERAPEUTICS 2015. [DOI: 10.1007/978-3-319-12730-9_1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Kolbe MF, Ribeiro FV, Luchesi VH, Casarin RC, Sallum EA, Nociti FH, Ambrosano GM, Cirano FR, Pimentel SP, Casati MZ. Photodynamic Therapy During Supportive Periodontal Care: Clinical, Microbiologic, Immunoinflammatory, and Patient-Centered Performance in a Split-Mouth Randomized Clinical Trial. J Periodontol 2014; 85:e277-86. [DOI: 10.1902/jop.2014.130559] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Reginato E, Wolf P, Hamblin MR. Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects. World J Immunol 2014; 4:1-11. [PMID: 25364655 PMCID: PMC4214901 DOI: 10.5411/wji.v4.i1.1] [Citation(s) in RCA: 128] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 12/20/2013] [Accepted: 02/18/2014] [Indexed: 02/05/2023] Open
Abstract
Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.
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Luchesi VH, Pimentel SP, Kolbe MF, Ribeiro FV, Casarin RC, Nociti FH, Sallum EA, Casati MZ. Photodynamic therapy in the treatment of class II furcation: a randomized controlled clinical trial. J Clin Periodontol 2013; 40:781-8. [DOI: 10.1111/jcpe.12121] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2013] [Indexed: 11/30/2022]
Affiliation(s)
- Vanessa H. Luchesi
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
| | - Suzana P. Pimentel
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
| | - Maria F. Kolbe
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
| | - Fernanda V. Ribeiro
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
| | - Renato C. Casarin
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
| | - Francisco H. Nociti
- Department of Prosthodontics and Periodontics; School of Dentistry at Piracicaba; University of Campinas (UNICAMP) Piracicaba; São Paulo Brazil
| | - Enilson A. Sallum
- Department of Prosthodontics and Periodontics; School of Dentistry at Piracicaba; University of Campinas (UNICAMP) Piracicaba; São Paulo Brazil
| | - Marcio Z. Casati
- Dental Research Division; School of Dentistry; Paulista University São Paulo; São Paulo Brazil
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Huang YY, Tanaka M, Vecchio D, Garcia-Diaz M, Chang J, Morimoto Y, Hamblin MR. Photodynamic therapy induces an immune response against a bacterial pathogen. Expert Rev Clin Immunol 2012; 8:479-94. [PMID: 22882222 DOI: 10.1586/eci.12.37] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
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.
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Affiliation(s)
- Ying-Ying Huang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
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18
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Milla Sanabria L, Rodríguez ME, Cogno IS, Rumie Vittar NB, Pansa MF, Lamberti MJ, Rivarola VA. Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment. Biochim Biophys Acta Rev Cancer 2012; 1835:36-45. [PMID: 23046998 DOI: 10.1016/j.bbcan.2012.10.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Revised: 09/28/2012] [Accepted: 10/01/2012] [Indexed: 12/31/2022]
Abstract
Photodynamic therapy (PDT) is a novel cancer treatment. It involves the activation of a photosensitizer (PS) with light of specific wavelength, which interacts with molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) that lead to tumor cell death. When a tumor is treated with PDT, in addition to affect cancer cells, the extracellular matrix and the other cellular components of the microenvironment are altered and finally this had effects on the tumor cells survival. Furthermore, the heterogeneity in the availability of nutrients and oxygen in the different regions of a tridimensional tumor has a strong impact on the sensitivity of cells to PDT. In this review, we summarize how PDT affects indirectly to the tumor cells, by the alterations on the extracellular matrix, the cell adhesion and the effects over the immune response. Also, we describe direct PDT effects on cancer cells, considering the intratumoral role that autophagy mediated by hypoxia-inducible factor 1 (HIF-1) has on the efficiency of the treatment.
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Affiliation(s)
- Laura Milla Sanabria
- Department of Molecular Biology, National University of Río Cuarto, Río Cuarto (5800), Córdoba, Argentina
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19
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Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J. Photodynamic therapy of cancer: an update. CA Cancer J Clin 2011; 61:250-81. [PMID: 21617154 PMCID: PMC3209659 DOI: 10.3322/caac.20114] [Citation(s) in RCA: 3530] [Impact Index Per Article: 252.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Patrizia Agostinis
- Department of Molecular Cell Biology, Cell Death Research & Therapy Laboratory, Catholic University of Leuven, B-3000 Leuven, Belgium,
| | - Kristian Berg
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway, ;
| | - Keith A. Cengel
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19004, USA, ;
| | - Thomas H. Foster
- Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA,
| | - Albert W. Girotti
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, 53226-3548, USA,
| | - Sandra O. Gollnick
- Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA,
| | - Stephen M. Hahn
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19004, USA, ;
| | - Michael R. Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114-2696, USA, ;
- Department of Dermatology, Harvard Medical School, Boston MA 02115
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
| | - Asta Juzeniene
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway, ;
| | - David Kessel
- Department of Pharmacology, Wayne State University School of Medicine, Detroit MI 48201, USA,
| | | | - Johan Moan
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway, ;
- Institute of Physics, University of Oslo, Blindern 0316 Oslo, Norway;
| | - Pawel Mroz
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114-2696, USA, ;
- Department of Dermatology, Harvard Medical School, Boston MA 02115
| | - Dominika Nowis
- Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Poland, ;
| | - Jacques Piette
- GIGA-Research, Laboratory of Virology & Immunology, University of Liège, B-4000 Liège Belgium,
| | - Brian C. Wilson
- Ontario Cancer Institute/University of Toronto, Toronto, ON M5G 2M9, Canada,
| | - Jakub Golab
- Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Poland, ;
- Institute of Physical Chemistry, Polish Academy of Sciences, Department 3, Warsaw, Poland
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20
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Mroz P, Hamblin MR. The immunosuppressive side of PDT. Photochem Photobiol Sci 2011; 10:751-8. [PMID: 21437314 PMCID: PMC3441049 DOI: 10.1039/c0pp00345j] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2010] [Accepted: 02/25/2011] [Indexed: 12/29/2022]
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.
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Affiliation(s)
- Pawel Mroz
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
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21
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Byun JY, Lee GY, Choi HY, Myung KB, Choi YW. The Expressions of TGF-β(1) and IL-10 in Cultured Fibroblasts after ALA-IPL Photodynamic Treatment. Ann Dermatol 2011; 23:19-22. [PMID: 21738358 DOI: 10.5021/ad.2011.23.1.19] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2010] [Revised: 07/07/2010] [Accepted: 08/29/2010] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was originally used for treating superficial skin tumors. The application of PDT to other inflammatory dermatoses like acne vulgaris, psoriasis, granuloma annulare, localized scleroderma and lichen sclerosus has recently been introduced. However, the underlying mechanisms are not well understood. We've previously reported the induction of tumor growth factor (TGF)-β(1) and interleukin (IL)-10 after PDT with ALA and intense pulsed light (IPL) in cultured HaCaT cells. OBJECTIVE The purpose of this study was to investigate the expressions of TGF-β(1) and IL-10 in cultured fibroblasts after PDT with using ALA and IPL. METHODS Cultured fibroblasts were treated with ALA-IPL PDT (1µmol/L of ALA; 0, 4, 8 and 12 J/cm(2) of IPL). The expressions of TGF-β(1) and IL-10 were investigated by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS TGF-β(1) mRNA and protein were reduced down to 0.52- and 0.63-fold, respectively, after PDT and the IL-10 protein was increased up to 2.74-fold after PDT. CONCLUSION The reduction of TGF-β(1) was prominent after PDT and so an antisclerotic effect can be expected after PDT. The induction of IL-10 may contribute to the anti-inflammatory effect, which explains the therapeutic benefit of PDT for inflammatory dermatoses.
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Affiliation(s)
- Ji Yeon Byun
- Department of Dermatology, School of Medicine, Ewha Womans University, Seoul, Korea
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22
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Brackett CM, Gollnick SO. Photodynamic therapy enhancement of anti-tumor immunity. Photochem Photobiol Sci 2011; 10:649-52. [PMID: 21253659 DOI: 10.1039/c0pp00354a] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Photodynamic therapy (PDT) is an FDA-approved modality for the treatment of early-stage disease and palliation of late-stage disease. Pre-clinical studies using mouse models and clinical studies in patients have demonstrated that PDT is capable of influencing the immune system. The effect of PDT on the generation of anti-tumor immunity is regimen-dependent and is tightly linked to the degree and nature of inflammation induced by PDT. However, the precise mechanism underlying PDT-regulated adaptive anti-tumor immunity remains unclear. This review will focus on the current knowledge of immune regulation by PDT.
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Affiliation(s)
- Craig M Brackett
- Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
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23
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Impact of photodynamic therapy on inflammatory cells during human chronic periodontitis. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2010; 101:348-54. [PMID: 20813541 DOI: 10.1016/j.jphotobiol.2010.08.007] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2010] [Revised: 08/06/2010] [Accepted: 08/10/2010] [Indexed: 12/14/2022]
Abstract
The aim of this study was to evaluate the effects of the photodynamic therapy (PDT) on the inflammatory infiltrate and on the collagen network organization in human advanced chronic periodontitis. Two different drug delivery systems (DDS) were tested (liposomes and nanoemulsions) to determine if the effects of PDT could differ according to the DDS used. Sixteen patients presenting two teeth with chronic advanced periodontitis and important tooth mobility with clinical indication of extraction were included in the group liposomes (group L, n=8) or in the group nanoemulsions (group N, n=8) in order to compare the effects of each DDS. Seven days before extractions one tooth of each patient was treated with PDT using phthalocyanine derivatives as photosensitizers and the contralateral tooth was taken as control. In group L the density of gingival collagen fibers (66±19%) was significantly increased (p<0.02) when compared to controls (35±21%). Concerning the antigen-presenting cells, PDT had differential effects depending on the drug delivery system; the number of macrophages was significantly decreased (p<0.05) in group L while the number of Langerhans cells was significantly decreased in group N (p<0.02). These findings demonstrate that PDT presents an impact on gingival inflammatory phenomenon during chronic periodontitis and leads to a specific decrease of antigen-presenting cells populations according to the drug delivery system used.
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Abstract
Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumors, resulting in cure of early disease and palliation of advanced disease. PDT was originally considered to be a local treatment; however, both pre-clinical and clinical studies have shown that local PDT treatment of tumors can enhance systemic anti-tumor immunity. The current state of investigations into the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this enhancement and the future of PDT as an immunotherapy are addressed in this review.
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25
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Ratkay LG, Waterfield JD, Hunt DW. Photodynamic therapy in immune (non-oncological) disorders: focus on benzoporphyrin derivatives. BioDrugs 2009; 14:127-35. [PMID: 18034564 DOI: 10.2165/00063030-200014020-00006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
This review examines the efficacy of photodynamic therapy in the treatment of immunological disorders. Photodynamic therapy (PDT) is a 2-step procedure. Firstly, a photosensitiser is introduced into the body, where it accumulates selectively in cells with elevated metabolism, such as cancer cells or activated cells of the immune system. Second, light is applied at a wavelength that excites the photosensitiser, producing a variety of short-lived oxygen-derived species. The effect is dependent on the doses of both photosensitiser and activating light. The mechanisms of action of PDT are multifactorial. Induction of high levels of oxidative stress results in necrotic cell death, while lower intensity oxidative stress initiates apoptosis. Sublethal doses may result in the modification of cell surface receptor expression levels and cytokine release and consequently influence cell behaviour. Immunomodulatory PDT (IPDT) utilises mainly apoptotic and sublethal doses. The studies reported here utilise verteporfin, a benzoporphyrin-derived chlorin-like photosensitiser. Veteporfin is a second generation photosensitiser, displaying rapid clearance and consequently a reduced period of skin photosensitivity compared with the first generation photosensitiser, porfimer sodium. In vivo studies showed that IPDT was effective in alleviating immunopathology in murine models of arthritis, contact hypersensitivity, experimental allergic encephalomyelitis and retention of allogeneic skin grafts. Based on these findings, early stage clinical trials with IPDT were initiated recently for the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis. While verteporfin has been the photosensitiser which pioneered IPDT, a new benzoporphyrin derivative photosensitiser, QLT0074, is under development. This has demonstrated an enhanced avidity for target cells as well as improved clearance characteristics.
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Affiliation(s)
- L G Ratkay
- QLT Inc, Vancouver, British Columbia, Canada.
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26
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Kabingu E, Oseroff AR, Wilding GE, Gollnick SO. Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy. Clin Cancer Res 2009; 15:4460-6. [PMID: 19549769 PMCID: PMC2805024 DOI: 10.1158/1078-0432.ccr-09-0400] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. EXPERIMENTAL DESIGN Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. RESULTS Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. CONCLUSIONS These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.
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Affiliation(s)
- Edith Kabingu
- PDT Center, Department of Cell Stress Biology, Buffalo, NY 14263
| | | | - Gregory E. Wilding
- Department of Biostatistics, Roswell Park Cancer Center, Elm and Carlton Sts., Buffalo, NY 14263
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27
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Byun JY, Choi HY, Myung KB, Choi YW. Expression of IL-10, TGF-beta(1) and TNF-alpha in Cultured Keratinocytes (HaCaT Cells) after IPL Treatment or ALA-IPL Photodynamic Treatment. Ann Dermatol 2009; 21:12-7. [PMID: 20548849 DOI: 10.5021/ad.2009.21.1.12] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2008] [Accepted: 08/05/2008] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Depending on the light dose and concentration of photosensitizer for photodynamic treatment (PDT), a multitude of dose-related events are demonstrable in PDT-treated cells. Sublethal doses may result in the alteration of cytokine release and consequently modify immune actions, rather than cause cell death. OBJECTIVE The purpose of this study was to investigate cytokine expression in cultured HaCaT cells after intense pulse light (IPL) treatment or PDT utilizing 5-aminolevulinic acid (ALA) and IPL at sublethal doses. METHODS Cultured HaCaT cells were treated with either IPL only (4, 8 and 12 J/cm(2)) or ALA-IPL PDT (100micromol/L of ALA; 0, 4, 8, and 12 J/cm(2) of IPL). The expression of IL-10, TGF-beta(1) and TNF-alpha was investigated by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS IL-10 protein increased up to 5.95-fold after IPL treatment and up to 2.85-fold after PDT. TGF-beta(1) mRNA and protein showed slight increases after both IPL treatment and PDT, of which the latter induced slightly larger increases. TNF-alpha mRNA and protein showed no induction or reduction after PDT. CONCLUSION Increased expressions of IL-10 and TGF-beta(1) was observed after PDT. The induction of IL-10 may contribute to the anti-inflammatory effect, which explains the therapeutic benefit of PDT for inflammatory dermatoses, and that of TGF-beta(1) may be related to the therapeutic effect for psoriasis. The finding that IL-10 induction was more marked after IPL treatment than after PDT suggests that other mechanisms than IL-10 induction in keratinocytes after PDT may participate in the anti-inflammatory effect of PDT.
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Affiliation(s)
- Ji Yeon Byun
- Department of Dermatology, School of Medicine, Ewha Womans University, Seoul, Korea
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28
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Ke MS, Xue LY, Feyes DK, Azizuddin K, Baron ED, McCormick TS, Mukhtar H, Panneerselvam A, Schluchter MD, Cooper KD, Oleinick NL, Stevens SR. Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4. Photochem Photobiol 2008; 84:407-14. [PMID: 18221452 DOI: 10.1111/j.1751-1097.2007.00278.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response.
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Affiliation(s)
- Malcolm S Ke
- Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH, USA
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Yusuf N, Katiyar SK, Elmets CA. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naive recipients. Photochem Photobiol 2008; 84:366-70. [PMID: 18208456 DOI: 10.1111/j.1751-1097.2007.00270.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4+ and CD8+ T cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, nontumor-bearing CD4 knockout (CD4-/-) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg kg(-1) Pc4, 110 J cm(-2) light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4-/- mice compared with WT mice. We next examined the role of CD8+ T cells in Pc4-PDT-induced immunosuppression using CD8-/- mice following the same treatment regimen used for CD4-/- mice. Similar to CD4-/- mice, CD8-/- mice exhibited less immunosuppression than WT mice. Pc4-PDT-induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (P < 0.05) and was mediated primarily by T cells, although macrophages were also found to play a role. Procedures that limit PDT-induced immunosuppression but do not affect PDT-induced regression of tumors may prove superior to PDT alone in promoting long-term antitumor responses.
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Affiliation(s)
- Nabiha Yusuf
- Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
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30
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Broady R, Yu J, Levings MK. Pro-tolerogenic effects of photodynamic therapy with TH9402 on dendritic cells. J Clin Apher 2008; 23:82-91. [DOI: 10.1002/jca.20162] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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31
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Calzavara-Pinton PG, Venturini M, Sala R. Photodynamic therapy: update 2006. Part 1: Photochemistry and photobiology. J Eur Acad Dermatol Venereol 2007; 21:293-302. [PMID: 17309449 DOI: 10.1111/j.1468-3083.2006.01902.x] [Citation(s) in RCA: 155] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new 'second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT.
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Affiliation(s)
- P G Calzavara-Pinton
- Department of Dermatology, Azienda Ospedaliera Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
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32
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Jiang H, Granville DJ, North JR, Richter AM, Hunt DWC. Selective Action of the Photosensitizer QLT0074 on Activated Human T Lymphocytes¶. Photochem Photobiol 2007. [DOI: 10.1562/0031-8655(2002)0760224saotpq2.0.co2] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Abstract
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.
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Affiliation(s)
- Ana P Castano
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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34
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Brown SB, Mellish KJ. Verteporfin: a milestone in opthalmology and photodynamic therapy. Expert Opin Pharmacother 2001; 2:351-61. [PMID: 11336591 DOI: 10.1517/14656566.2.2.351] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
During the past year, a photosensitiser named benzoporphyrin derivative (BPD) has been approved in 26 countries under the generic name verteporfin (Visudynetrade mark, Novartis), for the treatment of patients with a certain type of the wet form of age-related macular degeneration (AMD) by photodynamic therapy (PDT). AMD is the leading cause of blindness in the developed world, with approximately half a million new cases of the wet form per year. The approval of Visudynetrade mark therapy represents a major milestone in ophthalmology since AMD was previously untreatable by any modality which would preserve existing vision. It was also a milestone in the development of PDT, not only because it represented the first breakthrough in the use of PDT to treat an otherwise untreatable condition, but also because it represented the first mass market for a PDT treatment where prospects of a substantial financial return on many years of investment appear to be likely. In this article, we look at the background to the development of BPD, primarily for its use in AMD, but also in other applications.
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Affiliation(s)
- S B Brown
- Centre for Photobiology and Photodynamic Therapy, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
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Hunt DW, Chan AH. Influence of photodynamic therapy on immunological aspects of disease - an update. Expert Opin Investig Drugs 2000; 9:807-17. [PMID: 11060711 DOI: 10.1517/13543784.9.4.807] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Photodynamic therapy (PDT) utilises light-absorbing compounds combined with directed photo-irradiation to produce clinical effects. This review updates advances in the understanding of the biochemical pathways triggered by PDT within cells, its influence upon different immune parameters and progress in the use of PDT against human immune-mediated disease. Several works have further defined the notable capacity of PDT to foster anticancer immunity.
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Affiliation(s)
- D W Hunt
- QLT PhotoTherapeutics, Inc., 887 Great Northern Way, Vancouver, British Columbia V5T 4T5, Canada.
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Simkin GO, Tao JS, Levy JG, Hunt DW. IL-10 contributes to the inhibition of contact hypersensitivity in mice treated with photodynamic therapy. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2000; 164:2457-62. [PMID: 10679082 DOI: 10.4049/jimmunol.164.5.2457] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
We have explored the effect of photodynamic therapy (PDT) with verteporfin on the induction and expression of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in normal mice and IL-10-deficient mice. Our results indicate that DNFB sensitized mice given PDT with verteporfin and whole body red light irradiation exhibited a significant reduction in CHS compared with control animals. Administration of rIL-12 reversed the effect(s) of PDT as did treatment of mice with anti-IL-10-neutralizing Ab. Knockout mice deficient in IL-10 were found to be resistant to the inhibitory effects of PDT. In vitro proliferative responses using spleen cells from DNFB-sensitized and PDT-treated mice showed a significantly lower response to DNBS as compared with cells from DNFB-sensitized mice or DNFB and PDT-treated IL-10-deficient mice. Finally, naive mice exposed to PDT exhibited an increase in skin IL-10 levels, which peaked between 72 and 120 h post-PDT. Together these data support the role of IL-10 as a key modulator in the inhibition of the CHS response by whole body PDT.
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Affiliation(s)
- G O Simkin
- QLT PhotoTherapeutics Inc., Vancouver, BC, Canada.
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Honey CR, Obochi MO, Shen H, Margaron P, Yip S, Levy JG. Reduced xenograft rejection in rat striatum after pretransplant photodynamic therapy of murine neural xenografts. J Neurosurg 2000; 92:127-31. [PMID: 10616091 DOI: 10.3171/jns.2000.92.1.0127] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT The goal of this study was to develop a method of reducing neural xenograft rejection by pretreating the graft with photodynamic therapy (PDT). METHODS Xenograft cell suspensions were prepared from fetal mouse mesencephalon, after which they were incubated for 30 minutes with various concentrations of a photosensitizer, verteporfin for injection, and light exposure. The xenograft cell suspensions were injected into the dopamine-depleted striata of 40 hemiparkinsonian rats assigned to different treatment groups. Four weeks after transplantation, xenograft function (determined by methamphetamine-induced rotation) and survival (determined by immunohistochemical staining for murine neurons) were compared. Group 1 animals (xenografts pretreated with 25 ng/ml verteporfin) and Group 3 animals (no verteporfin pretreatment, but daily administration of cyclosporin A) had significantly better xenograft survival and function compared with control animals (no pretreatment with verteporfin). Group 2 animals (xenografts pretreated with 250 ng/ml verteporfin) had no significant improvement. CONCLUSIONS This work demonstrates improved neural xenograft survival and function when using pretransplant PDT of the graft in a rodent model. The potential benefits of this new therapy are its convenience (one pretransplant treatment) and its compatibility with host immunosuppression.
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Affiliation(s)
- C R Honey
- Department of Immunology and Microbiology, University of British Columbia, Vancouver, Canada.
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Nuclear factor-κB activation by the photochemotherapeutic agent verteporfin. Blood 2000. [DOI: 10.1182/blood.v95.1.256.001k29_256_262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The nuclear factor-kappa B (NF-κB) gene transactivator serves in the formation of immune, inflammatory, and stress responses. In quiescent cells, NF-κB principally resides within the cytoplasm in association with inhibitory κ (IκB) proteins. The status of IκB and NF-κB proteins was evaluated for promyelocytic leukemia HL-60 cells treated at different intensities of photodynamic therapy (PDT). The action of the potent photosensitizer, benzoporphyrin derivative monoacid ring A (verteporfin), and visible light irradiation were assessed. At a verteporfin concentration that produced the death of a high proportion of cells after light irradiation, evidence of caspase-3 and caspase-9 processing and of poly(ADP-ribose) polymerase cleavage was present within whole cell lysates. The general caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (ZVAD.fmk) effectively blocked these apoptosis-related changes. Recent studies indicate that IκB proteins may be caspase substrates during apoptosis. However, the level of IκBβ was unchanged for HL-60 cells undergoing PDT-induced apoptosis. IκB levels decreased during PDT-induced apoptosis, though ZVAD.fmk did not affect this change. At a less intensive level of photosensitization, cellular IκB levels were transiently depressed after PDT. At these times, p50 and RelA NF-κB species were increased within nuclear extracts, as revealed by electrophoretic mobility supershift assays. HL-60 cells transiently transfected with a κB-luciferase reporter construct exhibited elevated luciferase activity after PDT or treatment with tumor necrosis factor-, a well-characterized NF-κB activator. Productive NF-κB activation and associated gene transcription may influence the phenotype and behavior of cells exposed to less intensive PDT regimens. However, IκB is not subject to caspase-mediated degradation as a component of PDT-induced apoptosis. (Blood. 2000;95:256-262)
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Abstract
AbstractThe nuclear factor-kappa B (NF-κB) gene transactivator serves in the formation of immune, inflammatory, and stress responses. In quiescent cells, NF-κB principally resides within the cytoplasm in association with inhibitory κ (IκB) proteins. The status of IκB and NF-κB proteins was evaluated for promyelocytic leukemia HL-60 cells treated at different intensities of photodynamic therapy (PDT). The action of the potent photosensitizer, benzoporphyrin derivative monoacid ring A (verteporfin), and visible light irradiation were assessed. At a verteporfin concentration that produced the death of a high proportion of cells after light irradiation, evidence of caspase-3 and caspase-9 processing and of poly(ADP-ribose) polymerase cleavage was present within whole cell lysates. The general caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (ZVAD.fmk) effectively blocked these apoptosis-related changes. Recent studies indicate that IκB proteins may be caspase substrates during apoptosis. However, the level of IκBβ was unchanged for HL-60 cells undergoing PDT-induced apoptosis. IκB levels decreased during PDT-induced apoptosis, though ZVAD.fmk did not affect this change. At a less intensive level of photosensitization, cellular IκB levels were transiently depressed after PDT. At these times, p50 and RelA NF-κB species were increased within nuclear extracts, as revealed by electrophoretic mobility supershift assays. HL-60 cells transiently transfected with a κB-luciferase reporter construct exhibited elevated luciferase activity after PDT or treatment with tumor necrosis factor-, a well-characterized NF-κB activator. Productive NF-κB activation and associated gene transcription may influence the phenotype and behavior of cells exposed to less intensive PDT regimens. However, IκB is not subject to caspase-mediated degradation as a component of PDT-induced apoptosis. (Blood. 2000;95:256-262)
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