Cationic modified gold nanoparticles show enhanced gene delivery in vitro

Gold nanoparticles (AuNPs) can be suitably engineered for applications in gene delivery, and as carriers of peptides and proteins. They present innovative strategies in gene therapy for the treatment of genetic as well as acquired diseases. Optimisation of AuNPs in binding and the eventual release of the therapeutic agent in a controlled manner are crucial steps in the pathway to effective drug or gene therapy. In this study, we propose the formulation of cationic polymer [chitosan (Chit) and poly-l-lysine (PLL)] and cysteine (Cys)-coated AuNPs. These cationic AuNPs displayed good stability and resistance to aggregation under physiological conditions. All functionalised formulations remained in the size range 15.7-186 nm with narrow particle distributions and low polydispersity index (<0.9). Band shift and ethidium bromide intercalation assays determined the complexation of pDNA to the functionalised AuNP (FAuNP). Au-Chit/pDNA exhibited a significant 126% (p<0.01) cell viability in HepG2 cells, followed by Au-PLL/pDNA at 104% in HeLa cells and Au-cysteine/pDNA at 91.8% (p<0.001) in Caco-2 cells. Significant transgene activities in all cell lines were noted with enhanced gene expression for the FAuNP complexes over the cationic complexes on their own. The results of this study suggest that the low cytotoxicity and promising transgene activity of these FAuNPs, coupled with the ability to parametrically control particle size and surface properties, make these formulations suitable nanocarriers for drugs and genes.