pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection efficiency of nonviral gene vectors

摘要

A pH-responsive PEGylated nanogel was successfully prepared by means of emulsion copolymerization of 2-(N,N-diemylamino)ethyl methacrylate (AMA) with heterobifunctional poly(ethylene glycol) (PEG) bearing a 4-vinylbenzyl group at the alpha-end and a lactose moiety at the omega-end in the presence of potassium persulfate and ethyleneglycol dimethacrylate as a cross-linker.Polyplex micelle composed of PEG-block-poly(L-lysine) copolymer and plasmid DNA (PEG-Z>-PLL/pDNA) exhibited a far more efficient transfection ability in the presence of lacnanogel-8k-1.0% (PEG,M_n=8000;cross-linking density,1.0%) than the PEG-b-PLL/pDNA polyplex micelle alone (in the absence of lac-nanogel-8k-1.0%),suggesting that an appreciable fraction of lac-nanogel-8k-1.0% along with the PEG-b-PLL/pDNA polyplex micelle is taken up into the HuH-7 cells through the asialoglycoprotein receptor-mediated endocytosis process mediated by the cluster of a large number of lactose moieties on the surface of lac-nanogel-8k-1.0%,followed by the effective disruption of the endosome by the buffer effect of the unprotonated PAMA core in lac-nanogel-8k-1.0%.