Partially Acetylated Dendrimer-Entrapped Gold Nanoparticles with Reduced Cytotoxicity for Gene Delivery Applications

Abstract

Gene therapy has been concerned to be one of the most promising strategies to treat many diseases such as genetic disorders and cancer. However, design of safe and highly efficient gene delivery vectors still remains a great challenge. In this work, we report the use of partially acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for gene delivery applications. First, partially acetylated generation 5 poly(amidoamine) dendrimers with different acetylation degrees were used as templates to synthesize Au DENPs. The formed Au DENPs were characterized via different techniques and were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements, and the gene transfection efficiency was evaluated by Luc assay and fluorescence microscopic imaging of the EGFP expression, respectively. We show that despite the partial acetylation (5, 10, 20, and 30 acetyl groups per G5 dendrimer according to the molar feeding ratio), all acetylated Au DENPs are able to effectively compact the pDNA and transfect genes to the model cell line with high efficiency comparable to the Au DENPs without acetylation. With the proven less cytotoxicity of the partially acetylated Au DENPs than that of non-acetylated Au DENPs by cell viability assay, the developed partially acetylated Au DENPs may serve as promising vectors for safe gene delivery applications with non-compromised gene transfection efficiency.