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The Cooperative Anticancer Effect of Dual Styrenemaleic Acid Nano- Miceller System against Pancreatic Cancer

Khaled Greish, Katherine Muller, Julie IvanaJay and Don Haeng Lee

Pancreatic tumors remain one of the most formidable cancer types to treat. Patients with locally advanced or metastatic disease, which collectively represent over 80% of patients, rarely survive beyond one year. Pancreatic cancer is especially difficult to treat because of the uniqueness of its histology, with few vasculatures that can be used to supply anticancer agents. In this work we test a new system made of two styrene maleic acid (SMA) Nanomiceles encapsulating the phototosensetizer Zinc Protoporphyrin (ZnPP) or anticancer agent 4’-O-tetrahydropyranyl - doxorubicin (THP/Pirarubicin). Our hypothesis is that, local inflammatory response in tumor vessels induced by photosensitization can improve anticancer drug delivery and hence the anticancer activity. Two pancreatic tumor cell lines (Panc-1 and ASPC-1) were used to test the synergism of cytotoxic effect vitro. PANC-1 animal model in SCID mice were utilized to test the anticancer effect and the safety of the dual system in vivo . The photosensitizer activity of ZnPP nanomicelles followed by light irradiation and the administration of the anticancer micelles resulted in a synergetic antitumor effect in SCID mice in vivo but not in vitro . In conclusion, the dual Nanosystem of a photosensitizer and anticancer agent were well tolerated in animal model of pancreatic cancer and resulted in a synergistic anticancer effect. To our knowledge this is the first report of using a dual nanosystem of a photosensitizer and anticancer agent to treat pancreatic cancer.