Strategies for Enhanced Photodynamic Therapy Effects (original) (raw)
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Targeting Strategies in Photodynamic Therapy for Cancer Treatment
Handbook of Photomedicine, 2013
Despite recent advances in surgery, chemotherapy, and radiation treatment, survival of patients with advanced malignancy remains suboptimal. Photodynamic therapy is a relatively new cytotoxic treatment, predominantly used in anti-cancer approaches, that depends on the retention of photosensitizers in tumor and their activation after light exposure in the presence of molecular oxygen. Photosensitizers are photo-sensible compounds that upon photoactivation, effect strongly localized oxidative damage within the target cells. The ability to confine activation of the photosensitizer by restricting illumination to the tumor allows for a certain degree of selectivity. Nevertheless, the targeted delivery of photosensitizers to defined cells is a major challenge in photodynamic therapy of cancer, and one area of importance is photosensitizer targeting. In this sense, an arsenal of targeting strategies has been developed recently. Alterations or increased levels in receptor expression of specific cellular type occur in the diseased tissues. Therefore, photosensitizers can be covalently attached to molecules such as specific peptides, leading to a receptor-mediated targeting strategy. These active-targeting approaches may be particularly useful for vascular-targeted photodynamic therapy. The present chapter will focus on recent and significant advances and developments in targeting strategies in photodynamic therapy with the emphasis on target specificity.
Photodynamic therapy of cancer: An update
CA: A Cancer Journal for Clinicians, 2011
Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281
Photodynamic Therapy in the Treatment of Cancer: A review
Journal of Integrative Medicine
The search for non-invasive or minimally invasive approaches for the treatment of cancer has led to the development of different therapeutic regimes and one such regime is photodynamic therapy (PDT). PDT is a non-thermal treatment based on the synergy of three elements: the administration of a photosensitizer drug; light at a precise wavelength; and the presence of oxygen. When these three components are combined, they lead to the formation of reactive oxygen species (ROS), resulting in a complex cascade of events and subsequent cell death Studies revealed that PDT can prolong survival in patients with inoperable cancers and significantly improve the quality of life. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream strategy for cancer treatment. In this review, we have addressed the most important biological and physicochemical aspects of PDT, summarized its clinical status and provided an outlook for its potential fu...
Cell Death Pathways Associated with Photodynamic Therapy: An Update
Photochemistry and photobiology, 2018
Photodynamic therapy (PDT) has the potential to make a significant impact on cancer treatment. PDT can sensitize malignant tissues to light, leading to a highly selective effect if an appropriate light dose can be delivered. Variations in light distribution and drug delivery, along with impaired efficacy in hypoxic regions, can reduce the overall tumor response. There is also evidence that malignant cells surviving PDT may become more aggressive than the initial tumor population. Promotion of more effective direct tumor eradication is therefore an important goal. While a list of properties for the "ideal" photosensitizing agent often includes formulation, pharmacologic and photophysical elements, we propose that subcellular targeting is also an important consideration. Perspectives relating to optimizing PDT efficacy are offered here. These relate to death pathways initiated by photodamage to particular subcellular organelles.
Approaches to improve photodynamic therapy of cancer
2011
Introduction 3. Major advantages and disadvantages of PDT-what needs improvement or might be improved? 4. New photosensitizers 5. New light sources 6. Targeting cytoprotective mechanisms in PDT-treated cells 6.1. ROS-scavenging enzymes 6.2. Handling of damaged proteins 6.3. Mechanisms not directly associated with ROS scavenging 7. Combinations of PDT with other treatment modalities 8. Enhancement of PDT-mediated immune response 8.1. Immunoadjuvants 8.2. Cytokines 8.3. Adoptive immunotherapy 8.4. Introduction of foreign antigens 8.5. Anticancer therapeutics 9. Other new directions 9.1. Photochemical internalization 9.2. Metronomic PDT 9.3. Nanoparticle-based PDT 9.4. Two photon PDT 10. Conclusions 11. Acknowledgments 12. References Photodynamic therapy of cancer nanovehicle preparation for photodynamic therapy in vitro.
Photodynamic therapy of cancer. Basic principles and applications
Clinical & Translational Oncology, 2008
Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (λ≥600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen (1O2), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which 1O2 contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin®, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.
Direct tumor damage mechanisms of photodynamic therapy
Acta biochimica Polonica, 2005
Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer treatment regimen. It is a minimally invasive two-stage procedure that requires administration of a photosensitizing agent followed by illumination of the tumor with visible light usually generated by laser sources. A third component of PDT is molecular oxygen which is required for the most effective antitumor effects. In the presence of the latter, light of an appropriate wavelength excites the photosensitizer thereby producing cytotoxic intermediates that damage cellular structures. PDT has been approved in many countries for the treatment of lung, esophageal, bladder, skin and head and neck cancers. The antitumor effects of this treatment result from the combination of direct tumor cell photodamage, destruction of tumor vasculature and activation of an immune response. The mechanisms of the direct photodamage of tumor cells, the signaling pathways that lead to apoptosis or survival of sublethaly dam...
Photodiagnosis and Photodynamic Therapy, 2005
Photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as cancer therapy, some of its most successful applications are for non-malignant disease. The majority of mechanistic research into PDT, however, is still directed towards anti-cancer applications. In the final part of series of three reviews, we will cover the possible reasons for the well-known tumor localizing properties of photosensitizers (PS). When PS are injected into the bloodstream they bind to various serum proteins and this can affect their phamacokinetics and biodistribution. Different PS can have very different pharmacokinetics and this can directly affect the illumination parameters. Intravenously injected PS undergo a transition from being bound to serum proteins, then bound to endothelial cells, then bound to the adventitia of the vessels, then bound either to the extracellular matrix or to the cells within the tumor, and finally to being cleared from the tumor by lymphatics or blood vessels, and excreted either by the kidneys or the liver. The effect of PDT on the tumor largely depends at which stage of this continuous process light is delivered.
Photodynamic therapy in cancer treatment -an update review
Journal of Cancer Metastasis and Treatment , 2019
Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad update on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-ongoing clinical trials.
Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer
Cell death & disease, 2014
Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm(2), respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosi...