Novel polycationic micelles for drug delivery and gene transfer

Abstract

A series of amphiphilic cationic methoxy polyethylene glycol-b-poly{N-[3-(dimethylamino)propyl]methacrylamide-co-[2-hydroxylethylmethacrylate-poly(ε-caprolactone)]} {MPEG-b-P[NDAPM-co-(HEMA-PCL)]} polymers were synthesized by combining reversible addition–fragmentation chain transfer (RAFT) polymerization and the macromonomer method. The resulting polymers were able to self-assemble into micelles in water with a critical micellar concentration (CMC) in the range of 10–30 mg L⁻¹ and the CMC increased with the decrease in the PCL block content. It was found that the resulting polymers were able to form electrostatic complexes with plasmid DNA. The polymer–DNA complexes did not show apparent cytotoxicity in 293T cells. Importantly, the complexes exhibited good transfection efficiency in 293T cells at certain N/P ratios, while doxorubicin-loaded polymeric micelles also displayed controlled drug release. Besides, confocal microscopy showed that the drug and gene simultaneously carried by the cationic micelles could be delivered into the same cells, suggesting great potential for achieving the synergistic effect of drug and gene therapies.