Dendrimer-entrapped gold nanoparticles modified with β-cyclodextrin for enhanced gene delivery applications

Abstract

Generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers have been shown to be used as a highly efficient non-viral carrier in gene delivery. However, their high cytotoxicity and low gene transfection efficiency limit their practical applications in gene therapy. In order to improve their properties for enhanced gene delivery, the surfaces of G5 PAMAM dendrimers were grafted with β-cyclodextrin (β-CD) and were used as templates to entrap gold nanoparticles (Au NPs). The formed β-CD-modified dendrimer-entrapped Au NPs (Au DENPs-β-CD) and their ability to compact plasmid DNA (pDNA) were thoroughly characterized with different methods. The cytocompatibility of Au DENPs-β-CD was evaluated by cell viability assay. The gene delivery efficiency of the obtained Au DENPs-β-CD vector was tested by transfecting two different pDNAs encoding luciferase and enhanced green fluorescent protein into 293T cells (a human embryonic kidney cell line), respectively. Our results show that the Au DENPs-β-CD can compact the pDNA at an N/P ratio of 0.5 : 1 or above, possess less cytotoxicity than Au DENPs without β-CD conjugation, and enable more efficient cellular gene delivery than Au DENPs without β-CD conjugation. The developed Au DENPs-β-CD may hold great promise to be used as an efficient vector system for enhanced gene delivery applications.