Novel cationic hyperbranched polymers were prepared from 2-aminoethyl methacrylate (AEMA) and di(ethylene glycol) methyl ether methacrylate (DEGMA) via the reversible addition-fragmentation chain transfer (RAFT) polymerization for siRNA delivery. Non-degradable and acid-degradable hyperbranched polymers were synthesized using ,'-methylenebis(acrylamide) (MBAm) and 2,2-dimethacroyloxy-1-ethoxypropane (DEP) cross-linkers, respectively. Both types of polymers were capable of forming very stable nanosized polyplexes with siRNA. Epidermal growth factor receptor (EGFR) silencing of 95% was achieved with the acid degradable cationic hyperbranched polymer, and no significant cytotoxicity was observed. Our results confirmed the high potency of using such hyperbranched polymers for the efficient protection and delivery of siRNA.
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