Synthesis and characterization of biodegradable pH and reduction dual-sensitive polymeric micelles for doxorubicin delivery

Novel pH and reduction dual-sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy-poly(ethylene glycol)-b-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl) imidazole-l-aspartamide)] [mPEG-SS-P(BLA-co-APILA), MPBA] synthesized by a combination of ring-opening polymerization and side-chain reaction. The pH/reduction-responsive behavior of MPBA was observed by both dynamic light scattering and UV-vis experiments. The polymeric micelles and DOX-loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX-loaded micelles showed retarded drug release in phosphate-buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX-loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual-responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. (c) 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1771-1780