title: The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection.
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.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669, Singapore.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Chyan-Ying
authors.initials: CY
authors.lastname: Ke
authors.forename: Cyrus
authors.initials: C
authors.lastname: Weijie Beh
authors.forename: Shao-Qiong
authors.initials: SQ
authors.lastname: Liu
authors.forename: Suat-Hong
authors.initials: SH
authors.lastname: Goh
authors.forename: Yi-Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D000071228:Polyelectrolytes; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D002784:Cholesterol; D004247:DNA; D008823:Micelles; D011073:Polyamines; D000071228:Polyelectrolytes