Bioreducible Poly-L-Lysine-Poly[HPMA] Block Copolymers Obtained by RAFT-Polymerization as Efficient Polyplex-Transfection Reagents

Macromol Biosci. 2016 Jan;16(1):106-20. doi: 10.1002/mabi.201500212. Epub 2015 Jul 29.

Abstract

Polylysine-b-p[HPMA] block copolymers containing a redox-responsive disulfide bond between both blocks are synthesized by RAFT polymerization of pentafluorphenyl-methacrylate with a macro-CTA from Nϵ-benzyloxycarbonyl (Cbz) protected polylysine (synthesized by NCA polymerization). This polylysine-b-p[PFMA] precursor block copolymer is converted to polylysine(Cbz)-b-p[HPMA] by postpolymerization modification with 2-hydroxypropylamine. After removal of the Cbz protecting group, cationic polylysine-b-p[HPMA] copolymers with a biosplittable disulfide moiety became available, which can be used as polymeric transfection vectors. These disulfide linked polylysine-S-S-b-p[HPMA] block copolymers show low cytotoxicity and increased transfection efficiencies (HEK-293T cells) compared to analogous blockcopolymers without disulfide group making them interesting for the transfection of sensitive immune cells.

Keywords: RAFT-polymerization; bioreducible polyplexes; disulfide block copolymers; transfection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HEK293 Cells
  • Humans
  • Polylysine / analogs & derivatives
  • Polylysine / chemical synthesis
  • Polymerization
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymethacrylic Acids / chemical synthesis
  • Transfection / methods*

Substances

  • Polymers
  • Polymethacrylic Acids
  • polylysine-b-poly(2-hydroxypropyl methacrylamide) block copolymer
  • Polylysine