Eoganacht wrote: Photodynamic therapy photosensitizers and photoactivated chemotherapeutics exhibit distinct bioenergetic profiles to impact ATP metabolism Richard J. Mitchell - National Cancer Institute Frederick, USA
Dmytro Havrylyuk - North Carolina State University at Raleigh
Austin C. Hachey - University of Kentucky, USA
David K. Heidary - North Carolina State University at Raleigh, USA
Edith C. Glazer - North Carolina State University at Raleigh, USA. E-mail: eglazer@ncsu.ed
Received 11th August 2024
Accepted 18th November 2024
Introduction
Chemotherapy is part of the treatment regimen for approximately 60% of patients with cancer.1 However, traditional chemotherapies generally have dose-limiting adverse effects which have been associated with poor outcomes. Photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) have been developed to limit the tissues exposed to cytotoxic agents. In both types of phototherapy, light is used to activate a prodrug molecule.
For Ru(II) polypyridyl complexes, irradiation of the inactive complex induces excitation and population of the singlet metal to ligand charge transfer state (1MLCT), which then undergoes intersystem crossing, yielding the 3 MLCT state. In PDT, the chemical agents are photosensitizers (PSs) that undergo energy transfer from their triplet excited state to catalytically convert ground-state 3 O2 to reactive oxygen species (ROS), including 1 O2, via type I or type II electron and energy transfer processes.
2 PDT agents have shown significant translational utility, with porphyrin-based PSs in routine use in the clinic, and a new Ru(II)-based photosensitizer, TLD-1433, currently under evaluation in Phase II clinical trials3 with the FDA designating it with Fast Track status.
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A focused library of previously synthesized and reported Ru(II) molecules4,49,50,52–55 was used in this analysis. While other metal complexes are of interest to select research groups, we focused on Ru(II) polypyridyl complexes, due to their long-standing prominence in photochemical and photobiological studies, and their growing clinical significance for phototherapy applications, as evidenced by the success of TLD-1433. Moreover, in contrast to most other metal coordination compounds, Ru(II) complexes can act as either PDT or PACT agents with only slight structural changes.