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Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis.Proceedings of the National Academy of... Feb 2024Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of...
Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin () facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway. This mechanism is distinct from the well-established role of as a photodynamic therapy sensitizer in cells. Two analogs of , bearing different coordinated central metal cations, were also explored as controls. The first control, gadolinium texaphyrin (), is a weak photocatalyst but generates reactive oxygen species (ROS) efficiently. The second control, manganese texaphyrin (), is ineffective as both a photocatalyst and a ROS generator. Neither nor was found to trigger pyroptosis under the conditions where was active. Even in the presence of a ROS scavenger, treating MDA-MB-231 cells with at concentrations as low as 50 nM still allows for pyroptosis photo-activation. The present findings highlight how biomolecular photoredox catalysis could contribute to pyroptosis activation by mechanisms largely independent of ROS.
Topics: Pyroptosis; Reactive Oxygen Species; Metalloporphyrins
PubMed: 38381784
DOI: 10.1073/pnas.2314620121 -
Photodiagnosis and Photodynamic Therapy Mar 2021This article is a review of approaches to treatment of low and high-grade prostate cancer including a discussion of active treatment vs. active surveillance for patients... (Review)
Review
This article is a review of approaches to treatment of low and high-grade prostate cancer including a discussion of active treatment vs. active surveillance for patients with low-grade prostate cancer. In particular, we will review PDT as an option for active treatment of low-grade prostate cancer considered in light of recent clinical trials. The mechanism and clinical methods of PDT application and the key points from clinical trials using PDT for prostate cancer with the photosensitizers m-tetrahydroxyphenyl chloride, protoporphyrin IX, motexafin lutetium, padoporfin, and padeliporfin between the years 2002 and 2017 are reviewed. Recently developed methodologies for photodynamic prostate cancer treatment that are in the experimental stage, photodynamic diagnosis, fluorescence guided resection, and PSMA-targeted PDT will also be discussed.
Topics: Humans; Male; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms
PubMed: 33352313
DOI: 10.1016/j.pdpdt.2020.102158 -
Biomaterials Research 2018Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens... (Review)
Review
BACKGROUND
Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases.
INTRODUCTION
In presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure.
MAIN BODY
Up to dates, several PS were approved for clinical applications or under clinical trials. Photofrin® is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium (Photofrin®), Temoporfin (Foscan®), Motexafin lutetium, Palladium bacteriopheophorbide, Purlytin®, Verteporfin (Visudyne®), Talaporfin (Laserphyrin®) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development.
CONCLUSION
Here, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.
PubMed: 30275968
DOI: 10.1186/s40824-018-0140-z -
Oncotarget May 2017The search for new therapeutics for the treatment of prostate cancer is ongoing with a focus on the balance between the harms and benefits of treatment. New therapies... (Review)
Review
The search for new therapeutics for the treatment of prostate cancer is ongoing with a focus on the balance between the harms and benefits of treatment. New therapies are being constantly developed to offer treatments similar to radical therapies, with limited side effects. Photodynamic therapy (PDT) is a promising strategy in delivering focal treatment in primary as well as post radiotherapy prostate cancer. PDT involves activation of a photosensitizer (PS) by appropriate wavelength of light, generating transient levels of reactive oxygen species (ROS). Several photosensitizers have been developed with a focus on treating prostate cancer like mTHPC, motexafin lutetium, padoporfin and so on. This article will review newly developed photosensitizers under clinical trials for the treatment of prostate cancer, along with the potential advantages and disadvantages in delivering focal therapy.
Topics: Animals; Humans; Male; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Reactive Oxygen Species; Treatment Outcome
PubMed: 28430624
DOI: 10.18632/oncotarget.15496