Authors: J. Xu, M. Amiji
Affilation: Northeastern University, United States
Pages: 287 - 290
Keywords: gene therapy, targeting delivery, p53
More than 32,000 patients are diagnosed with pancreatic cancer in the United States per year and the disease is associated with very high mortality. Although gene therapy has tremendous promise, the major challenge has been in the development of safe and effective delivery system. The objective of this study is to develop novel gelatin based engineered nanovectors systems for efficient therapeutic gene delivery to pancreatic cancer. Control and EGFR targeted thiolated gelatin nanoparticles were prepared with efficient DNA encapsulation and stability. The particle sizes of all of these systems were in the range of 150-250 nm in diameter. Zeta potential has proved that this system is a neutral system. After proven for EGFR expression with Western blot analysis, Panc-1 cell line was choosen for the in vitro studies. In cytotoxicy study, both the control and the surface-modified nanoparticles were relatively less cytotoxic in Panc-1 cells as compared to PEI. Cell trafficking studies showed rapid uptake and plasmid release of EGFR-targeted nanoparticles in Panc-1 cells. Delivery of reporter plasmid DNA expressing with EGFR-targeted nanoparticles resulted in highest levels of GFP expression relative to other controls, including Lipofectin®-complexed DNA. With the same system, transfection with wt-p53 plasmid induced rapid apoptosis in Panc-1 cells. This project suggests that the EGFR-targeted thiolated gelatin nanoparticles can serve as a safe and efficient DNA delivery system for gene therapy as a treatment for pancreatic cancer.