Photodynamic therapy (PDT), a method that combines an organic photosensitizer and light to destroy tumors, was first used in the field of oncology more than 40 years ago. Despite its vast potential and some isolated success, PDT has failed to become a mainstream cancer treatment option. The sheer number of variables that must be optimized with respect to the light component, and the absence of large, comparative randomized clinical trials have been implicated. Another problem that has been largely ignored is the fact that singlet oxygen-mediated PDT requires a well-oxygenated environment. The most aggressive and drug-resistant cancers are hypoxic, thus, PDT with organic photosensitizers has fundamental limitations. Metallodrugs for light-mediated cancer therapy are an attractive alternative to their organic counterparts. These systems possess a variety of excited state configurations that can be accessed through rational and systematic changes to their very modular, yet structurally diverse, architectures. Such excited states can participate in both oxygen and oxygen-independent photobiological processes in catalytic and stoichiometric reactions, and offer many additional advantages over purely organic chromophores. Our group has led the development of both ruthenium- and osmium-based coordination complexes for photoactivated cancer therapy, with a lead compound entering human clinical trials for treating bladder cancer this year. Our multiwavelength agents that function regardless of oxygen tension enables treatment depth to match tumor invasion depth for personalized medicine. The path to this discovery and its future direction will be discussed.

Moving light-based cancer therapy from concept to reality with metallodrug photosensitizers

251st National Meeting (2016)

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