Enhanced gene transfection efficiency of PDMAEMA by incorporating hydrophobic hyperbranched polymer cores: effect of degree of branching

Abstract

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) is a well-known cationic polymer candidate for non-viral vectors for gene transfection. However, such an application has been greatly limited due to the cytotoxicity of the polymers. Herein, PDMAEMAs are grafted from hydrophobic hyperbranched PEHO cores (PEHO means poly(3-ethyl-3-(hydroxymethyl)-oxetane)), and the obtained hyperbranched multiarm copolymers of PEHO-g-PDMAEMAs show higher transfection efficiency than that of branched polyethylenimine (PEI) and PDMAEMA homopolymers, due to the improved cytotoxicity, DNA compaction, buffering ability and cellular uptake. In addition, to disclose the structure–property relationship, a series of PEHO-g-PDMAEMAs with different topological architectures are synthesized by changing the degrees of branching (DBs) of the PEHO cores and the lengths of the PDMAEMA arms. The ability of these vectors in DNA compaction, buffering ability, cytotoxicity and gene transfection efficiency is also investigated. It has been found the gene transfection efficiency of the vectors is dependent on the DB of the PEHO cores, but almost independent of the PDMAEMA arms in the experimental range.