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  • Title: PEGylated poly(2-(dimethylamino) ethyl methacrylate)/DNA polyplex micelles decorated with phage-displayed TGN peptide for brain-targeted gene delivery.
    Author: Qian Y, Zha Y, Feng B, Pang Z, Zhang B, Sun X, Ren J, Zhang C, Shao X, Zhang Q, Jiang X.
    Journal: Biomaterials; 2013 Mar; 34(8):2117-29. PubMed ID: 23245924.
    Abstract:
    Phage-displayed TGN peptide-decorated polymeric micelle-like polyplexes based on pegylated poly(2-(dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) were prepared for efficient brain-targeted gene delivery. The diblock copolymers Methoxy-PEG-PDMAEMA and Maleimide-PEG-PDMAEMA were synthesized by the atom transfer radical polymerization method. The TGN ligand, a 12-amino acid peptide that could facilitate blood-brain barrier (BBB) targeting, was conjugated to the PEG terminus of the copolymer via a maleimide-mediated covalent binding procedure. TGN-PEG-PDMAEMA was complexed with plasmid DNA to yield polyplexes. The physiochemical properties of the polyplexes, such as morphology, particle size, zeta potential, cytotoxicity and DNA complex formation ability, were studied prior to the successful in vitro and in vivo transfection. The TGN-PEG-PDMAEMA/DNA polyplexes maintained their stable nano-size, were characterized by good condensation capacity and low toxicity and even provided higher cellular uptake than the unmodified polyplexes (PEG-PDMAEMA/DNA polyplexes). Confocal microscopy studies showed that the DNA of TGN-PEG-PDMAEMA/DNA polyplexes entered into the nuclei through the endosome/lysosome pathway. The transfection efficiency of TGN-modified polyplexes was higher than that of unmodified polyplexes both in vitro and in vivo. The results obtained from frozen sections indicated the widespread expression of an exogenous gene in the mouse brain after intravenous injection. Therefore, the results demonstrate that the TGN-decorated PEG-PDMAEMA developed in this study could be utilized as a potential vehicle for gene delivery to the brain.
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