Controlled synthesis of pH responsive cationic polymers containing side-chain peptide moieties viaRAFT polymerization and their self-assembly

Abstract

A general and facile strategy was developed to prepare biocompatible peptide side-chain polymeric materials via reversible addition–fragmentation chain transfer (RAFT) polymerization. Three new dipeptide based monomers, Boc-Phe-Phe-oxyethyl methacrylate (Boc-FF-EMA), Boc-Ile-Phe-oxyethyl methacrylate (Boc-IF-EMA) and Boc-Val-Phe-oxyethyl methacrylate (Boc-VF-EMA), were synthesized and subsequently polymerized by RAFT process to afford well-defined peptide side-chain polymers, P(Boc-dipep-EMA), with controlled molecular weight, narrow polydispersity and precise chain end functionality. Further, a monomethoxy poly(ethylene glycol) (mPEG) based macro-chain transfer agent was employed for RAFT polymerization of these monomers to prepare well defined amphiphilic block copolymers, mPEG-b-P(Boc-dipep-EMA). Subsequent deprotection of side-chain Boc groups produced pH responsive homo- and block copolymers with primary amine moieties at the side chains. The cationic surface charge of various polymeric architectures was studied using dynamic light scattering (DLS) measurements. Atomic force microscopy (AFM) was employed to investigate the self-assembly of block copolymers. The in vitro biocompatibility to HeLa cells was investigated with these polymers to confirm their minimum cytotoxicity. These polymers have great potential for the pH-sensitive delivery of small interfering RNA (siRNA) owing to their interesting phase transition behaviour and biocompatibility.