Enhancement of transfection efficiency through rapid and noncovalent post-PEGylation of poly(dimethylaminoethyl methacrylate)/DNA complexes

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.