(273d) Nano-Photosensitizers for Photochemical Sensitization of Pancreatic Cancer to Chemotherapy

It is becoming increasingly clear that the complexity of cancer biology requires well-thought out, mechanistically sound combinations to address the problem of multiple and often compensatory pathways involved in cancer development and progression. Toward this end, we leverage nanotechnology to developed mechanism-guided, photodynamic therapy-based combination treatments. The goal of the current study is to demonstrate such a combination in orthotopic models of pancreatic cancer with photodynamic therapy and a recent clinically successful chemotherapeutic formulation (liposomal irinotecan). In orthotopic pancreatic cancer models, we demonstrate that low-dose photodynamic therapy and nanoliposomal irinotecan, working via three-way complementary mechanisms (reduced hypoxia, survivin and ABCG2 transporter) to control cancer compensatory pathways, dramatically inhibit tumor growth and prolong animal survival, offering immediate opportunities for clinical translation of pancreatic cancer treatment. Results from initial studies and mechanistic basis of the observed synergism along with clinical translation potential and a forward looking multi-agent nanoconstruct will be discussed.