Rambutan-like silica nanoparticles at tailored particle sizes for plasmid DNA delivery

Abstract

Silica nanoparticles (SNPs) have attracted widespread attention as biocompatible and efficient nanocarriers for gene delivery. The physicochemical properties of SNPs such as particle size, pore size, nanotopography and surface chemistry play important roles in regulating the intracellular delivery performance of genetic molecules. SNPs engineered with a rambutan-like spiky surface (Ram-SNPs) have shown significantly enhanced transfection efficiency for plasmid DNA (pDNA). However, the impact of the particle size of Ram-SNPs on their pDNA delivery performance has not been reported. Here, we synthesized Ram-SNPs with tailored nanoparticles sizes of 180, 330 and 520 nm by controlling the polymerization of resorcinol–formaldehyde and silica in a surfactant-free synthesis system. The polyethylenimine modified Ram-SNPs were loaded with pDNA molecules for intracellular delivery. Smaller sized Ram-SNPs demonstrated slightly weaker binding with pDNA, enhanced cellular uptake and significantly higher transfection efficiency than the larger particles. This structure–function relationship is different from other SNPs used for pDNA delivery. The cellular uptake mechanism by Ram-SNPs was also investigated. These findings provide useful guidance for the rational design of silica-based non-viral vectors for efficient gene delivery applications. A series of bioinspired rambutan-like silica nanoparticles with varied particle sizes were developed for plasmid DNA delivery, where smaller sized nanoparticles promoted the gene transfection efficiency due to enhanced cellular uptake capability.