Nanoemulsion-Assisted siRNA Delivery to Modulate the Nervous Tumor Microenvironment in the Treatment of Pancreatic Cancer
Ling Ding, Siyuan Tang, Ao Yu, Anlin Wang, Weimin Tang, Huizhen Jia, David Oupický
Abstract
Pancreatic cancer (PC) is a fatal human cancer, whose progression is highly dependent on the nervous tumor microenvironment. In the present study, cationic perfluorocarbon nanoemulsions were employed as an intraperitoneal delivery platform to facilitate the delivery and penetration of a therapeutic small interfering RNA (siRNA) to orthotopic pancreatic tumors. The nanoemulsion was used to silence the expression of the nerve growth factor (NGF) as a way of favorably modulating the tumor–neuronal interactions in pancreatic tumors. The nanoemulsions exhibited deep tumor penetration that was dependent on exocytosis and enhanced NGF gene silencing in vitro and in vivo when compared with control polycation/siRNA polyplexes, leading to the effective and safe suppression of tumor growth in orthotopic PC. Overall, emulsion-assisted delivery of NGF siRNA is a promising treatment approach for PC by targeting the interactions between the tumor cells and the nervous microenvironment.