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 N,N′-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.