Photodynamic therapy (PDT) is an approach to treating cancer that has the ability to selectively target tumors over healthy tissue. PDT employs a prodrug known as a photosensitizer (PS) combined with light and oxygen to facilitate localized cell death and has the potential to induce an antitumor immune response. The PDT effect is based on the generation of reactive molecular species (RMS), importantly singlet oxygen, from the triplet excited state of the PS. Historically, organic tetrapyrroles such as Photofrin have been used as PSs for PDT. Non-tetrapyrrolic metal complexes, although not approved for PDT, have become an area of intense focus over the past decade. The highly modular scaffold of certain metal complexes facilitates the tailoring of both the optical and photobiological properties of the PS to the specific type of cancer, permitting a tumor-centered approach to PS design for PDT. Ruthenium- and osmium-based PSs are particularly promising, with our own TLD1433 in Phase II clinical trials for the treatment of non-muscle invasive bladder cancer. This presentation will focus on the design, synthesis, and characterization of a series of next-generation metal-based PSs.

Development of novel metal-based photosensitizers for photodynamic therapy

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