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CA: a Cancer Journal For Clinicians 2011Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The... (Review)
Review
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.
Topics: Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents
PubMed: 21617154
DOI: 10.3322/caac.20114 -
Journal of Neuro-oncology Feb 2019Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for... (Review)
Review
INTRODUCTION
Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells.
MATERIALS/METHODS
A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs).
RESULTS
PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett's esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs.
CONCLUSION
PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.
Topics: Aminolevulinic Acid; Animals; Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Photochemotherapy; Photosensitizing Agents; Treatment Outcome
PubMed: 30659522
DOI: 10.1007/s11060-019-03103-4 -
ACS Nano May 2023Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive... (Review)
Review
Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT and PTT at the cellular, vascular and tumor microenvironmental levels, as well as translating both modalities in the clinic. Emerging evidence suggests that PDT and PTT may synergize due to their different mechanisms of action, and their nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations have gained momentum in recent years due to the development of multimodal nanoplatforms that simultaneously incorporate photodynamically- and photothermally active agents. In this review, we discuss how combining PDT and PTT can address the limitations of each modality alone and enhance treatment safety and efficacy. We provide an overview of recent literature featuring dual PDT/PTT nanoparticles and analyze the strengths and limitations of various nanoparticle design strategies. We also detail how treatment sequence and dose may affect cellular states, tumor pathophysiology and drug delivery, ultimately shaping the treatment response. Lastly, we analyze common experimental design pitfalls that complicate preclinical assessment of PDT/PTT combinations and propose rational guidelines to elucidate the mechanisms underlying PDT/PTT interactions.
Topics: Humans; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Nanomedicine; Phototherapy; Neoplasms; Nanoparticles; Cell Line, Tumor
PubMed: 37129253
DOI: 10.1021/acsnano.3c00891 -
Journal For Immunotherapy of Cancer Jan 2021The past decade has witnessed major breakthroughs in cancer immunotherapy. This development has been largely motivated by cancer cell evasion of immunological control... (Review)
Review
The past decade has witnessed major breakthroughs in cancer immunotherapy. This development has been largely motivated by cancer cell evasion of immunological control and consequent tumor resistance to conventional therapies. Immunogenic cell death (ICD) is considered one of the most promising ways to achieve total tumor cell elimination. It activates the T-cell adaptive immune response and results in the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). In this review, we first discuss the role of PDT based on several classes of photosensitizers, including porphyrins and non-porphyrins, and critically evaluate their potential role in ICD induction. We emphasize the emerging trend of ICD induction by PDT in combination with nanotechnology, which represents third-generation photosensitizers and involves targeted induction of ICD by PDT. However, PDT also has some limitations, including the reduced efficiency of ICD induction in the hypoxic tumor microenvironment. Therefore, we critically evaluate strategies for overcoming this limitation, which is essential for increasing PDT efficiency. In the final part, we suggest several areas for future research for personalized cancer immunotherapy, including strategies based on oxygen-boosted PDT and nanoparticles. In conclusion, the insights from the last several years increasingly support the idea that PDT is a powerful strategy for inducing ICD in experimental cancer therapy. However, most studies have focused on mouse models, but it is necessary to validate this strategy in clinical settings, which will be a challenging research area in the future.
Topics: Animals; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Immunogenic Cell Death; Neoplasms; Photochemotherapy; Photosensitizing Agents; Precision Medicine
PubMed: 33431631
DOI: 10.1136/jitc-2020-001926 -
Molecules (Basel, Switzerland) Jun 2021Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a... (Review)
Review
Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and "phenomenological" nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (O). The damaging action of O on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine O photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.
Topics: Animals; Antiviral Agents; Humans; Membrane Lipids; Photosensitizing Agents; Singlet Oxygen; Viral Envelope; Virus Diseases; Viruses
PubMed: 34209713
DOI: 10.3390/molecules26133971 -
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 -
Molecules (Basel, Switzerland) Jul 2019The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential... (Review)
Review
The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.
Topics: Animals; Glycoconjugates; Humans; Magnetic Resonance Imaging; Mice; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Positron-Emission Tomography; Singlet Oxygen; Theranostic Nanomedicine; Water
PubMed: 31340553
DOI: 10.3390/molecules24142669 -
Journal of the American Chemical Society Nov 2023Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to... (Review)
Review
Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As a consequence, they have been used, in general, for building dynamic molecular systems responsive to light but, more particularly, in the field of oncology, as prodrugs for a new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, the ability of a coordination bond to be selectively broken under visible light irradiation offers fascinating perspectives in oncology: it is possible to make poorly toxic agents in the dark that become activated toward cancer cell killing by simple visible light irradiation of the compound inside a tumor. In this Perspective, we review the most important concepts behind the PACT idea, the relationship between ruthenium compounds used for PACT and those used for a related phototherapeutic approach called photodynamic therapy (PDT), and we discuss important questions about real-life applications of PACT in the clinic. We conclude this Perspective with important challenges in the field and an outlook.
Topics: Humans; Ruthenium; Coordination Complexes; Photochemotherapy; Light; Neoplasms; Antineoplastic Agents; Photosensitizing Agents
PubMed: 37846939
DOI: 10.1021/jacs.3c01135 -
Future Medicinal Chemistry Sep 2019Tetracyclines are well established antibiotics but show phototoxicity as a side effect. Antimicrobial photodynamic inactivation uses nontoxic dyes combined with harmless... (Review)
Review
Tetracyclines are well established antibiotics but show phototoxicity as a side effect. Antimicrobial photodynamic inactivation uses nontoxic dyes combined with harmless light to destroy microbial cells by reactive oxygen species. Tetracyclines (demeclocycline and doxycycline) can act as light-activated antibiotics by binding to bacterial cells and killing them only upon illumination. The remaining tetracyclines can prevent bacterial regrowth after illumination has ceased. Antimicrobial photodynamic inactivation can be potentiated by potassium iodide. Azide quenched the formation of iodine, but not hydrogen peroxide. Demeclotetracycline (but not doxycycline) iodinated tyrosine after light activation in the presence of potassium iodide. Bacteria are killed by photoactivation of tetracyclines in the absence of oxygen. Since topical tetracyclines are already used clinically, blue light activation may increase the bactericidal effect.
Topics: Anti-Bacterial Agents; Bacteria; Light; Photochemotherapy; Photosensitizing Agents; Tetracyclines
PubMed: 31544504
DOI: 10.4155/fmc-2018-0513 -
Cells Nov 2023Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of... (Review)
Review
Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy's broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.
Topics: Humans; Photosensitizing Agents; Phototherapy; Photochemotherapy; Anti-Infective Agents; Acne Vulgaris
PubMed: 37998399
DOI: 10.3390/cells12222664