Pancreatic Cancer Gene Therapy with EGFR-Targeted Gelatin-Based Nanoparticle Systems

Pancreatic Cancer Gene Therapy with EGFR-Targeted Gelatin-Based Nanoparticle Systems

Student: Padmaja Magadala
Department: Pharmaceutical Sciences
Advisor: Mansoor Amiji

Abstract

Over the last few decades, the incidence of pancreatic cancer has risen to become the fourth leading cause of cancer deaths, in both males and females, in the western world. The vague manifestation of its symptoms, in addition to the lack of specific and early diagnostic procedures, further complicate the approaches to successful therapy of pancreatic ductal adenocarcinoma (PDAC). At the molecular level, while mutations in p53 cause over 50% of solid tumors in humans, over-expression of the epidermal growth factor receptor (EGFR) has been implicated in the poor prognosis and clinical outcome in pancreatic cancer.
Novel approaches to increase safety and therapeutic efficiency of non-viral gene delivery agents for cancer therapy have gained wide-spread attention in recent years. Current efforts in this direction are focused on using biocompatible materials, which can be efficiently directed to accumulate in the tissue and/or cell of interest with the use of targeting ligands.
The main objective of this project is to develop and characterize a novel EGFR-targeted gelatin-based engineered nanoparticulate system for safe and efficient in vitro and in vivo therapeutic plasmid DNA delivery in pancreatic cancer. EGFR-targeting peptide is conjugated to the surface of gelatin nanoparticles via a PEG-spacer to accomplish longer circulation time and cell-specific targeting of nanoparticles for in vivo applications. Plasmid DNA expressing wild-type p53 tumor suppressor protein will be encapsulated and the therapeutic effect will be evaluated in an orthotopic Panc-1 pancreatic cancer xenograft model.