Acetalated-dextran as valves of mesoporous silica particles for pH responsive intracellular drug delivery

Abstract

A pH-sensitive drug release system using acetalated-dextran as valves was designed to manipulate smart intracellular release of anticancer drugs. Dextran was grafted onto the exterior of MSN through a click reaction, and followed by acetalation to generate the final carriers of MSN–Dex-Ac. The hydrophobic Dex-Ac would act as valves on the MSN surface to block the entrapped drugs inside the MSN pores. While under acidic conditions mimicking the micro-environment of endosomal/lysosomal compartments, the valves could be opened by acetal hydrolysis to recover the acetalated-dextran to its hydrophilic state, resulting in fast drug release. In vitro drug release profile clearly showed that DOX release was restricted at pH 7.4 by the valves, while it was accelerated under acidic conditions. Fast endocytosis and intracellular DOX release was observed by confocal laser scanning microscopy (CLSM). Cytotoxicity evaluation showed good biocompatibility with the carriers. In vitro MTT assays revealed that the DOX-loaded particles exhibited comparable antitumor activity with free DOX towards HeLa cells.