Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery.
Well-defined pentablock copolymers (PBPs) of P(HEMA)-b-P(DMAEMA)-b-PEG-b-P(DMAEMA)-b-P(HEMA) (in which PEG=poly(ethylene glycol), P(DMAEMA)=poly((2-dimethyl amino)ethyl methacrylate), and P(HEMA)=poly(2-hydroxyethyl methacrylate)), with different block lengths of P(DMAEMA), for non-viral gene delivery were prepared via consecutive atom transfer radical polymerizations (ATRPs) from the same di-2-bromoisobutyryl-terminated PEG (Br-PEG-Br) center block. The PBPs demonstrate good ability to condense plasmid DNA (pDNA) into 100-160 nm size nanoparticles with positive zeta potentials of 25-35 mV at PBPs/pDNA weight ratios of 5-25. The PBPs exhibit very low in vitro cytotoxicity and excellent gene transfection efficiency in HEK293 and COS7 cells. In particular, the transfection efficiencies of all the PBPs in HEK293 cells are comparable to, or higher than those of polyethylenimine (PEI, 25 kDa) at most weight ratios. The ability of the copolymers to condense plasmid DNA and the transfection efficiency of the resulting complexes are dependent on the chain length of P(DMAEMA) blocks. In addition to reducing the cytotoxicity and increasing the stability of the plasmid complexes, the PEG center block and the short P(HEMA) end blocks also help to enhance the gene transfection efficiency. Thus, the approach to well-defined block copolymers via ATRP provides a versatile means for tailoring the structure of non-viral gene vectors to meet the requirements of low cytotoxicity, good stability and high transfection capability for gene therapy applications.
Xu
Fu-Jian
FJ
Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 119260, Singapore.
Li
Hongzhe
H
Li
Jun
J
Zhang
Zhongxing
Z
Kang
En-Tang
ET
Neoh
Koon-Gee
KG
D000818:Animals; D002460:Cell Line; D006801:Humans; D008689:Methacrylates / Q000008:administration & dosage*; D017348:Microscopy, Electron, Scanning Transmission; D009757:Nylons; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011102:Polyhydroxyethyl Methacrylate / Q000008:administration & dosage*; D014162:Transfection / Q000379:methods*
D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D011102:Polyhydroxyethyl Methacrylate; D011092:Polyethylene Glycols