Lactobionic acid-chitosan functionalised gold-coated poly(lactide-co-glycolide) nanoparticles for hepatocyte targeted gene delivery

Abstract

Abstract Nanoscale non-viral gene delivery vectors are attractive systems for the efficient and safe delivery of therapeutic genes. This study explored the potential of surface tailored poly(lactide-co-glycolide) (PLGA) systems for targeted gene delivery to human hepatocellular carcinoma (HepG2) cells overexpressing the asialoglycoprotein receptor (ASGPR). Chitosan (CS) functionalised gold (G) PLGA nanoparticles (NPs) were synthesised with and without the targeting ligand, lactobionic acid (LA), and bound to pCMV-Luc-DNA (pDNA) to form nanocomplexes. NPs were physicochemically characterised, and pDNA binding and protection by the NPs were investigated using mobility shift, dye displacement and nuclease digestion assays. MTT and luciferase assays served to evaluate cytotoxicity and transgene expression in vitro. Nanocomplexes of 20–40 nm in size effectively protected the DNA from nuclease digestion and exhibited low cytotoxicity (>90% cell viability). Targeted transgene expression was significantly greater than the untargeted expression, confirming ASPGR uptake. Our results highlight the potential of these hybrid CS-PLGA based nano-platforms for targeted gene therapy, warranting further development, especially for liver-directed gene therapy.