Abstract B028: Development of targeted photoactivable liposomes for PDT-based combination therapy in ovarian cancer

Introduction: Approximately 70% of patients with ovarian cancer are diagnosed at an advanced stage with widespread peritoneal metastasis. The current standard treatment usually involves cytoreductive surgery followed by platinum-taxane-based chemotherapy. However, despite initial responses, nearly 70% of patients experience disease recurrence within five years, largely due to the development of chemotherapy resistance. To address these challenges, combination cancer therapies have emerged as a promising approach, aiming to target tumor-specific survival pathways and effectively counteract resistance mechanisms. Methods: We engineered a targeted nanotechnology platform that integrates photodynamic therapy (PDT) with drug-repurposing strategies to treat microscopic tumors. Our innovative combinatorial formulation co-encapsulates clinically used DNA-damaging agents and DNA-repair inhibitors within a single liposome system. In vitro efficacy and in vivo studies were conducted using an orthotopic xenograft model of ovarian peritoneal carcinomatosis. Results: The formulation achieved high loading efficiency and facilitated the preferential delivery of synergistic drug concentrations to tumor cells. This approach selectively targets epithelial ovarian cancer cells, enhancing DNA damage accumulation and inhibiting tumor growth with the combination of PDT and chemotherapy. Additionally, in vivo studies showed higher accumulation of the formulation in metastatic tumor sites and dose-dependent improvement in survival compared to untreated mice. This enhanced efficacy is likely due to the potent drug combinations maintaining their synergistic effects in circulation. Conclusion: Overall, this study investigates the potential role of PDT-based combination therapies in addressing multidrug resistance by targeting DNA repair pathways and highlights their strong potential for clinical translation. Citation Format: Payal Srivastava, Carla Arnau del Valle, Anika Dasgupta, Riley Thomas. Schoch, Sumiao Pang, Kaitlyn Ann. Moore, Brian Schnoor, Dana Roque, Huang Chiao Huang. Development of targeted photoactivable liposomes for PDT-based combination therapy in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B028.