Photodynamic therapy (PDT) is a strategy for treating cancer that employs a photosensitizer (PS), light, and oxygen to destroy tumors and tumor vasculature with spatiotemporal control. The PDT mechanism involves activation of the PS light to produce a triplet excited state that sensitizes the formation of reactive molecular species (RMS) that are ultimately responsible for eliciting cytotoxic effects. Porphyrins and other tetrapyrrolic structures have historically been PSs of choice for PDT, with Photofrin being the first (and in many countries the only) approved PS. Recently, metallodrug PSs have gained attention due to their tunable physicochemical and photophysical properties and variety of excited state configurations with potential for enhanced anticancer activity. Our own TLD1433, a Ru(II) polypyridyl complex incorporating a key oligothienyl unit, in currently in Phase 2 clinical trials (NCT03945162) for treating non-muscle invasive bladder cancer (NMIBC) with PDT. In this work, we report the design and development of a new class of metallodrug PSs, which are structurally related to TLD1433, and investigate their photochemical and photobiological properties.

Metallodrug photosensitizers for light-based cancer therapy

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