The Role of Spacer Segments in Increasing the Transfection Efficacy of Au-Core Polymeric-Shell Nanoparticulate Gene Vectors

The surface chemistry of gold nanoparticles is a key determinant of their final biological properties. In this study, we investigated the influence of the PEG chain length, positioned between the gold core and the cationic polymer, on the transfection efficiency in HeLa and HGF cell lines. Two types of nonviral vectors were synthesized from the same AuNPs, which were subsequently functionalized with PEG of 1000 and 2500 Da, respectively. Onto these PEG chains, identical copolymeric sequences of PEI2000-PEG500-GA were covalently attached to provide quasi-shielding (via PEG500) and enable tumor targeting/accumulation (via GA). Both vectors demonstrated that such functionalization enhances cellular uptake and targeting specificity while exhibiting excellent DNA delivery efficiency, minimal <i>in vitro</i> cytotoxicity, and no detectable <i>in vivo</i> adverse effects following intravenous administration in animal models. A superior loading capacity was observed when the PEG linked to the gold core was 2500 Da, suggesting a contribution from solvation-driven interactions.