Endosomal-Escape Polymers Based on Multicomponent
Reaction-Synthesized Monomers Integrating Alkyl and Imidazolyl Moieties
for Efficient Gene Delivery
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Abstract
As
one of the toughest tasks in the course of intracellular therapeutics
delivery, endosomal escape must be effectively achieved, particularly
for intracellular gene transport. In this report, novel endosomal-escape
polymers were designed and synthesized from monomers by integrating
alkyl and imidazolyl via Passerini reaction and reversible addition–fragmentation
chain transfer polymerization (RAFT). After introducing the endosomal-escape
polymers with proper degrees of polymerization (DPs) into poly(2-dimethylaminoethyl
methacrylate) (PDMAEMA) as the gene delivery vectors, the block copolymers
exhibited significantly enhanced hemolytic activity at endosomal pH,
and the plasmid DNA (pDNA)-loaded polyplexes showed efficient endosomal
escape compared with PDMAEMA, ultimately achieving dramatically increased
gene transfection efficacy. These results suggest that the polymers
that integrate alkyl and imidazolyl moieties for efficient endosomal
escape have wide potential applications for intracellular gene delivery