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Frontiers in Chemistry 2021Photodynamic 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... (Review)
Review
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 ( enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.
PubMed: 34178948
DOI: 10.3389/fchem.2021.691697 -
Journal of Clinical Medicine Oct 2019Photodynamic therapy (PDT) involves the selective sensitization of tissues to light. A major advance in the field occurred when Thomas Dougherty at the Roswell Park... (Review)
Review
Photodynamic therapy (PDT) involves the selective sensitization of tissues to light. A major advance in the field occurred when Thomas Dougherty at the Roswell Park Cancer Institute initiated a series of clinical studies that eventually led to FDA approval of the procedure. This report contains a summary of Dougherty's contributions and an assessment of where this has led, along with a summary of implications for future drug development.
PubMed: 31581613
DOI: 10.3390/jcm8101581 -
Journal of the National Cancer Institute Jun 1998Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by... (Review)
Review
Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Dihematoporphyrin Ether; Humans; Inflammation; Neoplasms; Photochemotherapy; Photosensitizing Agents
PubMed: 9637138
DOI: 10.1093/jnci/90.12.889 -
Future Oncology (London, England) Jun 2010Photodynamic therapy (PDT) is a tumor-ablative and function-sparing oncologic intervention. The relative simplicity of photosensitizer application followed by light... (Review)
Review
Photodynamic therapy (PDT) is a tumor-ablative and function-sparing oncologic intervention. The relative simplicity of photosensitizer application followed by light activation resulting in the cytotoxic and vasculartoxic photodynamic reaction has allowed PDT to reach a worldwide audience. With several commercially available photosensitizing agents now on the market, numerous well designed clinical trials have demonstrated the efficacy of PDT on various cutaneous and deep tissue tumors. However, current photosensitizers and light sources still have a number of limitations. Future PDT will build on those findings to allow development and refinement of more optimal therapeutic agents and illumination devices. This article reviews the current state of the art and limitations of PDT, and highlight the progress being made towards the future of oncologic PDT.
Topics: Aminolevulinic Acid; Dihematoporphyrin Ether; Forecasting; Humans; Mesoporphyrins; Nanoparticles; Neoplasms; Oxygen; Photochemotherapy; Photosensitizing Agents
PubMed: 20528231
DOI: 10.2217/fon.10.51 -
TheScientificWorldJournal Jun 2004Bladder cancer treatment remains a challenge despite significant improvements in preventing disease progression and improving survival. Intravesical therapy has been... (Review)
Review
Bladder cancer treatment remains a challenge despite significant improvements in preventing disease progression and improving survival. Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e. Ta, T1, and carcinoma in situ) with specific objectives which include treating existing or residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival regardless of the treatment. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Intravesical chemotherapy reduces short-term tumor recurrence by about 20%, and long-term recurrence by about 7%, but has not reduced progression or mortality. Presently, BCG immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, T1, CIS) and reduces tumor recurrence, disease progression, and mortality. Interferons, Keyhole-limpet hemocyanin (KLH), bropirimine and Photofrin-Photodynamic Therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in therapy for superficial TCC.
Topics: Administration, Intravesical; Antineoplastic Agents; BCG Vaccine; Carcinoma, Transitional Cell; Cytosine; Dihematoporphyrin Ether; Hemocyanins; Humans; Interferons; Photochemotherapy; Secondary Prevention; Urinary Bladder Neoplasms
PubMed: 15349563
DOI: 10.1100/tsw.2004.81 -
Integrative Cancer Therapies 2023Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including...
Two Molecular Weights Holothurian Glycosaminoglycan and Hematoporphyrin Derivative-Photodynamic Therapy Inhibit Proliferation and Promote Apoptosis of Human Lung Adenocarcinoma Cells.
Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.
Topics: Humans; Molecular Weight; Adenocarcinoma of Lung; Lung Neoplasms; Apoptosis; Glycosaminoglycans; Hematoporphyrin Derivative; Photochemotherapy; Cell Proliferation
PubMed: 36624619
DOI: 10.1177/15347354221144310 -
Photodiagnosis and Photodynamic Therapy Sep 2015What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve... (Review)
Review
INTRODUCTION
What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve standard of care.
PURPOSE
The questions we wish to answer are: where are we clinically with PDT, why is it not standard of care, and what is being done in clinical trials to get us there.
METHOD
Rather than a meta-analysis or comprehensive review, our review focuses on who the major research groups are, what their approaches to the problem are, and how their results compare to standard of care. Secondary questions include what the effective depth of light penetration is, and how deep can we expect to kill tumor cells.
CURRENT RESULTS
A measurable degree of necrosis is seen to a depth of about 5mm. Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but need an adequate Phase III trial. Talaporfin with cavitary light application appears promising, although only a small case series has been reported. Foscan for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results were improved over controls, but are poor compared to other groups. 5-Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over controls, but the comparison to standard of care is still poor.
CONCLUSION
Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued.
Topics: Aminolevulinic Acid; Brain Neoplasms; Cell Death; Clinical Trials as Topic; Fluorescence; Hematoporphyrin Derivative; Humans; Infratentorial Neoplasms; Mesoporphyrins; Nitric Oxide; Photochemotherapy; Photosensitizing Agents; Porphyrins; Signal Transduction; Surgery, Computer-Assisted
PubMed: 25960361
DOI: 10.1016/j.pdpdt.2015.04.009 -
FEBS Letters Nov 1984Hematoporphyrin derivative, used in photodynamic therapy of cancer, was found to generate the cysteinyl free radical as seen by spin-trapping. Oxygen appears to be an...
Hematoporphyrin derivative, used in photodynamic therapy of cancer, was found to generate the cysteinyl free radical as seen by spin-trapping. Oxygen appears to be an absolute requirement for thiyl radical production. Singlet oxygen may be the initiating species since azide inhibits oxygen uptake and radical production. In addition, the hydroxyl radical, or a radical with similar reactivity, is also observed and is proposed as the precursor for thiyl free radical production.
Topics: Cysteine; Electron Spin Resonance Spectroscopy; Free Radicals; Hematoporphyrin Derivative; Hematoporphyrins; Light; Photochemistry; Radiation-Sensitizing Agents; Sulfur
PubMed: 6094251
DOI: 10.1016/0014-5793(84)81303-4 -
Anticancer Research 2007Sonodynamic therapy (SDT) of cancer is based on preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and subsequent... (Review)
Review
Sonodynamic therapy (SDT) of cancer is based on preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and subsequent activation of the drug by ultrasound irradiation. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer. This is a unique advantage in the non-invasive treatment of nonsuperficial tumors when compared to laser light used for photodynamic therapy. Recently, it has been found that photochemically active porphyrins also show significant antitumor effects when activated with ultrasound. The mechanism of sonodynamic action has been suggested to involve photoexcitation of the sensitizer by sonoluminescent light, with subsequent formation of singlet oxygen. This mini-review provides a brief overview of the following four sonosensitizers useful in SDT: i) a homogeneous complex of oligomers of hematoporphyrin, Photofrin II; ii) a gallium porphyrin complex, ATX-70; iii) a hydrophilic chlorin derivative, A7X-S10, and iv) a novel porphyrin derivative devoid of photosensitivity, DCPH-P-Na (I).
Topics: Animals; Dihematoporphyrin Ether; Hematoporphyrins; Mice; Models, Biological; Neoplasms; Photosensitizing Agents; Porphyrins; Rats; Ultrasonic Therapy; Ultrasonics
PubMed: 17970027
DOI: No ID Found -
Photomedicine and Laser Surgery Aug 2013Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source... (Review)
Review
OBJECTIVE
Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients.
MATERIALS AND METHODS
Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures.
RESULTS
Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional.
CONCLUSIONS
Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies.
Topics: Aminolevulinic Acid; Dihematoporphyrin Ether; Hematoporphyrin Photoradiation; Humans; Intense Pulsed Light Therapy; Lasers; Occupational Exposure; Occupational Health; Photochemotherapy; Photosensitizing Agents; Porphyrins; Safety Management; Verteporfin
PubMed: 23859750
DOI: 10.1089/pho.2013.3496