Development of novel gene delivery system for cancer therapy

Abstract

In this thesis, novel biodegradable charged polyester-based vectors (BCPVs) were designed and synthesized as siRNA carrier for cancer treatment. Under optimized conditions, the BCPV can effectively protect siRNA from degradation by RNase in the serum, and would subsequently promote intracellular siRNA uptake via endocytosis. The formulation and usage of BCPV-based siRNA carriers cause significant inhibition of targeted abnormal proto‐oncogenes expression in adherent growth cells (pancreatic cancer cell line) and non-adherent growth cells (leukemia cell line), resulting in obvious inhibition of cancer cell bioactivity. In addition, BCPV was able to simultaneously co-deliver K-ras and Notch1 siRNA into pancreatic cancer cells to overcome chemotherapeutic drug resistance (Gemcitabine) by reversing the epithelial-mesenchymal transition (EMT). Lastly, BCPV, as modifying polymer, was used to coat the surface of graphene quantum dots (GQDs) for fabrication of multifunctional siRNA and drug co-delivery systems, which realized real-time monitoring of the delivery efficacy and distribution of the drugs and siRNA.