7401 Development and Evaluation of Ruthenium-based Photoactivated Chemotherapeutic Agents

Abstract Disclosure: A. Wilson: None. B. Cejudo: None. K. Enkhbold: None. Y. Chung: None. S. Chiaino: None. M.R. Norris: None. J. Pollock: None. Photoactivated Chemotherapy (PACT) represents an opportunity to limit the off-target toxicity inherent to traditional chemotherapies. Selective activation of toxic effects would allow effective chemical treatment of solid tumors without the normally associated side effects. Expanding on previous work in our lab (1), we have evaluated the potential of ruthenium-based compounds as PACT agents by testing light activation, cell viability in breast cancer and lung cancer cells, biocompatibility, and DNA interactions. We have observed that active ruthenium-complexes with increased lipophilicity tend to be more toxic to the cancer cells. In addition, we have ligated known anticancer compounds (2) to our ruthenium cages, evaluated the capacity to mask the general cytotoxic effects, and examined the release of a fully active drug after light exposure. We can successfully release the active drugs with light, but when using light at 450 nm it takes about six hours of direct exposure in a cuvette to see successful conversion. We are currently systematically exploring different wavelengths of light to reduce activation time and increase potential clinical utility (3). Once optimal wavelengths are determined, cancer cell viability experiments will be performed in the absence and presence of light in order to evaluate the therapeutic window for these ruthenium-complexes. References: (1) Paul, L. et. al. J. Inorg. Biochem.2022, 235: 111930. (2) Peerzada, M. N. et. al. Eur. J. Med. Chem.2018, 155: 13-23. (3) Dunkel, P. & Ilaš, J. T. Cancers2021, 13: 40-42. Presentation: 6/2/2024