[en] Purpose. The aim of this work was to develop a new strategy to introduce poly(ethylene glycol) (PEG) into methacrylate-based polymer/ DNA complexes in order to produce hemocompatible particles able to transfect cells in the presence of serum. Methods. Atom transfer radical polymerization was used to synthesize a well-defined poly(2-(dimethylamino) ethyl methacrylate) homopolymer ( PDMAEMA) and a poly( 2-( dimethylamino) ethyl methacrylate-b-poly( ethylene glycol) alpha-methyl ether, omega-methacrylate) palm-tree-like copolymer (P(DMAEMA-b-MAPEG)). The complexes obtained by self assembly of the pCMVbeta plasmid and the polymers were used to transfect Cos-7 cells. Their physical properties - particle size and zeta potential - were characterized respectively by dynamic light scattering and electrophoretic mobility measurements. Ex vivo hemocompatibility was also determined. Results. The PDMAEMA/pCMVbeta complexes transfected Cos-7 cells exclusively in the absence of serum. Although the P(DMAEMA-b-MAPEG) copolymer had no transfection activity per se, the addition of the latter to pre-formed PDMAEMA/DNA complexes significantly enhanced the activity and allowed transfection even in the presence of serum. The presence of palm-tree - like copolymers also improved the hemocompatibility properties of the complexes. No effect on platelet counts was observed for P(DMAEMA-b-MAPEG)/ pCMVbeta complexes, whereas a decrease of platelets was clearly observed when blood cells were incubated with PDMAEMA/pCMVbeta complexes. Conclusions. Such a synergistic effect of noncovalent PEGylation of poly( amino methacrylate)/ DNA complexes allows a new and versatile approach to tune up transfection efficiency.
Research center :
CEIB - Centre Interfacultaire des Biomatériaux - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology Chemistry
Author, co-author :
Pirotton, S.
Muller, Caroline; Université de Liège - ULiège
Pantoustier, N.
Botteman, F.
Collinet, B.
Grandfils, Christian ; Université de Liège - ULiège > Biochimie et physiologie générale
Dandrifosse, Guy ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Degée, Philippe; Université de Liège - ULiège
Dubois, Philippe ; Université de Liège - ULiège > Centre d'études et de rech. sur les macromolécules (CERM)
Raes, M.
Language :
English
Title :
Enhancement of transfection efficiency through rapid and noncovalent post-PEGylation of poly(dimethylaminoethyl methacrylate)/DNA complexes
Publication date :
August 2004
Journal title :
Pharmaceutical Research
ISSN :
0724-8741
eISSN :
1573-904X
Publisher :
Kluwer Academic/Plenum Publ, New York, United States - New York
Volume :
21
Issue :
8
Pages :
1471-1479
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Nouveaux polycations et vectorisation d’ADN dans les cellules de parois vasculaires” Convention Région Wallonne n° 14612, année 2001-2004 dans le cadre du concours Initiative 2000
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