Photodynamic therapy (PDT) is a promising approach to cancer treatment that remains underutilized despite its inherent spaciotemporal selectivity towards cancerous tissue. PDT uses a non-toxic prodrug, or photosensitizer (PS) that, in the presence of light and oxygen, produces cytotoxic reactive oxygen species (ROS) to trigger cell death mechanisms. Approved PSs for cancer therapy are comprised of tetrapyrrolic structures that sensitize singlet oxygen. We believe that PDT could become a more accessible alternative or adjuvant therapy with the development of next-generation PSs. Metal-based PSs are of particular interest due to their relative ease of synthesis and tunable photophysical and physicochemical properties. Ruthenium and osmium polypyridyl PSs serve as examples, with our own TLD1433 currently being in phase II clinical trials for the treatment of non-muscle invasive bladder cancer (Clinicaltrials.gov identifier NCT03945162). This presentation will highlight the application of rational molecular design to metallodrug PS development for PDT.

Rational design of metallodrug photosensitizers for photodynamic therapy

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