Thermally sensitive polypeptide-based copolymer for DNA complexation into stable nanosized polyplexes

摘要

Gene therapy based on non-viral synthetic delivery vectors has attracted much attention in the past two decades. However, it is still in clinical trial stages, mainly due to the lack of safe and efficient delivery vehicles. Herein, we report on the synthesis and DNA complexation ability of novel, hybrid copolymer comprising poly(N-isopropylacrylamide) (PNIPAm) block with poly(ethylene glycol) (PEG) side chains and a polycationic block of poly(l-lysine) (PLLys). The copolymer was synthesized in a two-step procedure. In the first step, a thermally sensitive PNIPAm-g-PEG copolymer with terminal ammonium hydrochloride group was prepared. The second step involves controlled ring-opening polymerization of Z-l-lysine N-carboxyanhydride initiated by the PNIPAm-g-PEG macroinitiator. The hybrid copolymer obtained show high ability to condense DNA into stable polyplexes with sizes below 100 nm. Cytotoxicity evaluation of both hybrid copolymer and its polyplex with DNA indicates that it might be a good candidate for gene-delivery applications.