6533b836fe1ef96bd12a0822

RESEARCH PRODUCT

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

Kristof TappertzhofenEvelyn MontermannKaloian KoynovMatthias BrosRudolf ZentelDavid HuesmannSimone BeckMatthias Barz

subject

Polymers and PlasticsCationic polymerizationBioengineering02 engineering and technologyTransfection010402 general chemistry021001 nanoscience & nanotechnology01 natural sciences0104 chemical sciencesBiomaterialschemistry.chemical_compoundchemistryPolymerizationPolylysinePolymer chemistryMaterials ChemistryCopolymerMoietyReversible addition−fragmentation chain-transfer polymerization0210 nano-technologyProtecting groupBiotechnology

description

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.

https://doi.org/10.1002/mabi.201500212