Dendrimer-entrapped gold nanoparticles modified with folic acid for targeted gene delivery applications

We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) as a non-viral vector for targeted gene delivery applications. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with FA via covalent conjugation were used as templates to synthesize gold nanoparticles with an Au salt/dendrimer molar ratio of 25 : 1. The synthesized FA-modified Au DENPs (Au DENPs-FA) were used as a non-viral vector for the delivery of plasmid DNA (pDNA) into a model cancer cell line (HeLa cells) overexpressing high-affinity FA receptors (FAR). The DNA compaction ability of the formed Au DENPs-FA was systematically characterized using a gel retardation assay, zeta potential, and dynamic light scattering. We show that similar to the Au DENPs vector without FA, the Au DENPs-FA vector was able to compact the pDNA encoding enhanced green fluorescent protein (EGFP) at an N/P ratio of 0.5. Transfection results show that the Au DENPs-FA vector enables much higher luciferase and EGFP gene expression in HeLa cells overexpressing FAR than the Au DENPs without FA, demonstrating the role played by FA-mediated targeting for enhanced gene transfection in target cells. With a lower cytotoxicity than that of the Au DENPs without FA proven by a cell viability assay, the developed FA-modified Au DENPs may be used as a promising non-viral vector for safe and targeted gene therapy applications.