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 ( M n =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.