Lipid-gold-nanoparticle hybrid-based gene delivery.

Gene delivery holds promise to cure many inheritable or acquired diseases that are currently considered incurable. Liposomes are clinically well-established drug-delivery vehicles with promising properties, including biocompatibility, high drug-to-carrier ratios, and straightforward drug-encapsulation capability. However, widespread clinical use of this delivery system still requires better delivery efficiency and lower cytotoxicity. It is a daunting task to develop the optimum delivery system with minimum toxicity and maximum delivery efficiency because toxicity and delivery efficiency often increase or decrease simultaneously. Recently developed nanomaterial-based delivery schemes, which enable precise physical and chemical control of nanoscale structures, hold great promise in addressing these problems. In particular, it has been demonstrated that gold nanoparticles (AuNPs) serve as excellent vehicles for the delivery of genetic materials into cells. A gene-delivery system based on AuNPs would be especially attractive because the particles can be readily conjugated with targeting biomolecules as well as genes at high packing densities, and this high packing density facilitates high delivery efficiency and low enzymatic degradation of modified DNA strands. Moreover, AuNPs are neither highly toxic nor strongly immunogenic. Here, we devise lipid-DNA-AuNP (L-DNA-AuNP) hybrid-based gene delivery system for better transfection efficiency and reduced cytotoxicity by taking advantages of both AuNPs and liposomes as gene-delivery vehicles (Figure 1). DNA strands loaded onto AuNPs are supported and stabilized, and more DNA strands are delivered per delivery event. These factors enhance transfection efficiency. However, negatively charged DNA strands are exposed in this form; this negative charge deteriorates the contact between DNA-AuNPs and cells because the cell membrane is also weakly negatively charged. This could be overcome by attaching a cationic lipid layer to DNA-modified AuNP.