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From the journal: Chemical Science Submitted 15 Jul 2020
Accepted 04 Sep 2020
First published 09 Sep 2020 Near-infrared Absorbing Ru(II) Complexes Act as Immunoprotective Photodynamic Therapy (PDT) Agents Against Aggressive Melanoma Liubov Lifshits, John A Roque III, Prathyusha Konda, Susan Monro, Houston D. Cole, David von Dohlen, Susy Kim, Gagan Deep, Randolph P. Thummel, Colin G. Cameron, Shashi Gujar and Sherri Ann McFarland PDF 1. INTRODUCTION
Photodynamic therapy (PDT) is an approved anticancer modality where light is used to activate an otherwise nontoxic photosensitizer (PS) to generate cytotoxic reactive oxygen species (ROS) through energy (Type II) or electron (Type I) transfer. Type II formation of 1O2 is thought to be the major contributor to the antitumor photodynamic effect, arising from three synergistic mechanisms: direct cytotoxicity toward tumor cells, damage to tumor vasculature, and induction of an inflammatory response that can stimulate systemic antitumor immunity.1–13
PDT is delivered in two stages: local or systemic administration of a PS, followed by light delivery to the site of the primary tumor. The light can be delivered virtually anywhere in the body with today’s flexible fiber optic devices, and interstitial PDT (i-PDT) techniques can even be used to physically implant the fibers directly inside tumors.14 The overall PDT response is determined by the PDT regimen, which includes the PS dose as well as the light treatment (wavelength, fluence, and irradiance),15,16 and can be tuned to enhance local or systemic effects.16
The most recent preclinical and clinical studies have shown that, apart from its direct tumor-destroying capacity, PDT can perform immunomodulatory functions. Specifically, PDT stimulates both innate and adaptive immune responses, destroying distant untreated tumor cells (at either primary or metastatic sites) and leading to the development of antitumor immunity that can prevent cancer recurrence.15,17–28
Such therapy-induced antitumor immunological benefits form the foundation of modern-day cancer immunotherapies. Thus, local PDT has much unrealized promise, and has the potential to be an important adjuvant in multimodal cancer therapy..
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4. CONCLUSIONS
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This study shows that 2-PDT (with clinically-approved red light) destroys melanoma cells directly as well as indirectly by ICD-mediated generation of anti-tumor immune responses. Additional studies are underway to explore the optimum PDT regimen (including NIR wavelengths) and to delineate the therapeutic potential and understand the different immune cell mediators involved. Overall, these results identify compound 2 as a PS that could potentially be used for eliciting systemic effects through local delivery of melanoma PDT.