Reduction-sensitive amphiphilic copolymers made via multi-component Passerini reaction for drug delivery

One-step synthesis of amphiphilic polymers containing disulfide bond within the hydrophobic backbone was demonstrated via multi-component Passerini reaction. The obtained polymer was self-assembled into micelles in aqueous solution. Curcumin (CUR), an effective and safe anticancer agent, which was limited by its water insolubility and poor bioavailability, was loaded into the micelles as a model drug. The nanoscale polymeric micelles were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Faster intracellular CUR release was observed by confocal laser scanning microscopy (CLSM) in the HeLa cells pretreated with GSH than in the unpretreated ones. Micelles also loaded with NH2-BODIPY which was almost non-fluorescent and gave strong enhanced fluorescence under acid conditions. The phenomenon of the stronger enhanced fluorescence in the pretreated HeLa cells showed further that the obtained polymer was reduction-sensitive. In vitro MTT assays showed that the micelles were biocompatible and CUR-loaded micelles had higher cellular proliferation inhibition in contrast to free CUR toward HeLa cells. These results highlight the potential of using multi-component Passerini reaction to make functional copolymers as smart nanocarriers for drug delivery. (C) 2014 Elsevier B.V. All rights reserved.