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Title: The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection
Authors: Wang, Y.
Ke, C.-Y.
Weijie Beh, C.
Liu, S.-Q. 
Goh, S.-H. 
Yang, Y.-Y.
Keywords: Cationic polymer micelles
Gene transfection
Issue Date: Dec-2007
Citation: Wang, Y., Ke, C.-Y., Weijie Beh, C., Liu, S.-Q., Goh, S.-H., Yang, Y.-Y. (2007-12). The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection. Biomaterials 28 (35) : 5358-5368. ScholarBank@NUS Repository.
Abstract: Cationic micelles self-assembled from a biodegradable amphiphilic copolymer, poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate} (P(MDS-co-CES)) have recently been reported for efficient gene delivery and co-delivery of drug and nucleic acid. In this study, poly(ethylene glycol) (PEG) of various molecular weights (Mn=550, 1100 and 2000) was conjugated to P(MDS-co-CES) having different cholesterol grafting degrees to improve the stability of micelle/DNA complexes in the blood for systemic in vivo gene delivery. DNA binding ability, gene transfection efficiency and cytotoxicity of P(MDS-co-CES), PMDS, PEGylated PMDS and PEGylated P(MDS-co-CES) micelles were studied and compared. As with P(MDS-co-CES), PEG-P(MDS-co-CES) polymers could also self-assemble into stable micelles of small size. However, PMDS and PEG-PMDS without cholesterol could not form stable micelles but formed large particles. PEGylation of polymers significantly decreased their gene transfection efficiency in HEK293, HepG2, HeLa, MDA-MB-231 and 4T1 cells. However, increasing N/P ratio promoted gene transfection. An increased cholesterol grafting degree led to greater gene expression level possibly because of the more stable core-shell structure of the micelles. PEG550-P(MDS-co-CES) micelles induced high gene transfection level, comparable to that provided by P(MDS-co-CES) micelles. PEGylated polymers were much less cytotoxic than P(MDS-co-CES). PEGylated P(MDS-co-CES) micelles may provide a promising non-viral vector for systemic in vivo gene delivery. © 2007 Elsevier Ltd. All rights reserved.
Source Title: Biomaterials
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2007.08.013
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