Abstract LB241: Development of a photoactivatable platform to optimize delivery of platinum chemotherapy in advanced women's cancers

Abstract Patients with metastatic ovarian and triple-negative breast cancers have low overall survival. One limitation to the effective treatment of these cancers is that they don’t have targeted treatment options and therefore are highly dependent on cytotoxic chemotherapy, including highly toxic DNA damaging agents like oxaliplatin. A major limitation of these DNA-targeted drugs is that they have deleterious effects in both cancerous and non-cancerous cells. This toxicity leads to serious adverse side effects which can limit the duration of treatment and decrease a patient’s quality of life.We previously developed a water-soluble polymer functionalized with oxidized oxaliplatin that is released by photoactivation by blue-violet light at 400 nm to allow for the localized, temporal release of chemotherapy. Although this construct promoted the light-dependent cytotoxicity of ovarian cancer cells, this activation did not occur when the polymer was preloaded in the cancer cells and was only observed by activation in the extracellular environment. Herein we describe the development of an optimized platform, M1, that promotes photoactivatable cytotoxicity within breast and ovarian cancer cells. Photoactivation of M1 occurs at 600 nm, a wavelength of light with greater tissue penetration. We found that the photoactivation of M1 was sufficient to kill both ovarian and breast cancer cells independent of oxaliplatin delivery. Moreover, this cytotoxicity required preloading of M1 into cancer cells as extracellular photoactivation was not sufficient to kill cancer cells. These results highlight the potential of M1 to be a photoactivatable therapeutic agent in aggressive metastatic cancers. Future efforts will focus on strategies to enrich M1 uptake in cancer cells as compared to the surrounding normal tissue, which would allow for increased cytotoxic specificity necessary for in vivo and clinical applications. Funding supported by the San Antonio Medical Foundation and supported by NRSA T32 GM148752. Citation Format: Jycole Bush, Kanyashree Jana, Isai Ramos, Nancy Wilkinson, Kirk Schanze, April Risinger. Development of a photoactivatable platform to optimize delivery of platinum chemotherapy in advanced women's cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB241.