A Zwitterionic-Shielded Carrier with pH-Modulated Reversible Self-Assembly for Gene Transfection.
Cationic vectors are ideal candidates for gene delivery thanks to their capability to carry large gene inserts and their scalable production. However, their cationic density gives rise to high cytotoxicity. We present the proper designed core-shell polyplexes made of either poly(ethylene imine) (PEI) or poly(2-dimethylamino ethyl methacrylate) (PDMAEMA) as the core and zwitterionic poly(acrylic acid)-block-poly(sulfobetaine methacrylate) (PAA-b-PSBMA) diblock copolymer as the shell. Gel retardation and ethidium bromide displacement assays were used to determine the PEI/DNA or PDMAEMA/DNA complexation. At neutral pH, the copolymer serves as a protective shell of the complex. As PSBMA is a nonfouling block, the shell reduced the cytotoxicity and enhanced the hemocompatibility (lower hemolysis activity, longer plasma clotting time) of the gene carriers. PAA segments in the copolymer impart pH sensitivity by allowing deshielding of the core in acidic solution. Therefore, the transfection efficiency of polyplexes at pH 6.5 was better than at pH 7.0, from β-galactosidase assay, and for all PAA-b-PSBMA tested. These results were supported by more favorable physicochemical properties in acidic solution (zeta potential, particle size, and interactions between the polymer and DNA). Thus, the results of this study offer a potential route to the development of efficient and nontoxic pH-sensitive gene carriers.
R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University , Chung-Li, Taoyuan 320, Taiwan.
Yuju
Y
Shih
R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University , Chung-Li, Taoyuan 320, Taiwan.
Antoine
0000-0002-0383-695X
A
Venault
R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University , Chung-Li, Taoyuan 320, Taiwan.|School of Chemical Engineering and Chemistry, Mapúa Institute of Technology , Intramuros, Manila 1002, Philippines.
Lemmuel L
LL
Tayo
R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University , Chung-Li, Taoyuan 320, Taiwan.
Sheng-Han
SH
Chen
Department of Chemical and Materials Engineering, National Central University , Jhong-Li, Taoyuan 320, Taiwan.|Department of Botany and Microbiology, College of Science, King Saud University , P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Akon
A
Higuchi
IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095, Montpellier, France.
Andre
A
Deratani
Department of Botany and Microbiology, College of Science, King Saud University , P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Arunachalam
A
Chinnathambi
Department of Botany and Microbiology, College of Science, King Saud University , P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Sulaiman Ali
SA
Alharbi
IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095, Montpellier, France.
Damien
D
Quemener
R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University , Chung-Li, Taoyuan 320, Taiwan.|Department of Botany and Microbiology, College of Science, King Saud University , P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Yung
0000-0003-1419-4478
Y
Chang
D004247:DNA; D018014:Gene Transfer Techniques; D006863:Hydrogen-Ion Concentration; D007097:Imines / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D009757:Nylons / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D007097:Imines; D008689:Methacrylates; D009757:Nylons; D011095:Polyethylenes; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); C505405:poly(ethylene imine); D004247:DNA