Synthesis and characterization of cationic micelles self-assembled from a biodegradable copolymer for gene delivery.
We have recently reported biodegradable cationic micelles self-assembled from an amphiphilic copolymer, poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl)methyl bis(ethylene)ammonium bromide]sebacate} (P(MDS-co-CES)), which were utilized to deliver a drug and nucleic acid simultaneously, and a synergistic effect was achieved. In this paper, synthesis and characterization of the polymer is presented in details, focusing on micelle formation and DNA binding under various conditions, cytotoxicity, in-vitro degradation, and gene transfection in various cell lines. The polymer was degradable and formed micelles at very low concentrations even in an environment with high salt concentration. These micelles fabricated at pH 4.6 had an average size of less than 82 nm and zeta potential of up to 84 +/- 5 mV, displaying strong DNA binding ability. They induced high gene expression efficiency in various cell lines, which was significantly greater than poly(ethylenimine) (PEI) especially in 4T1 mouse and MDA-MB-231 human breast cancer cell lines, but they were less cytotoxic. These cationic micelles may provide a promising nonviral vector for gene delivery.
Wang
Yong
Y
Institute of Bioengineering and Nanotechnology, 31 Biopolis, The Nanos, #04-01, Singapore 138669.
Wang
Li-Shan
LS
Goh
Suat-Hong
SH
Yang
Yi-Yan
YY
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002412:Cations; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*
D001672:Biocompatible Materials; D002412:Cations; D008823:Micelles; D011108:Polymers