Redox-Responsive Supramolecular Micelles for Targeted Imaging and Drug Delivery to Tumor

Abstract: The tumor-selective drug delivery system based on supramolecular micelles that were self-assembled by amphiphilic beta-cyclodextrins (beta-CD) with redox-responsiveness and fluorescence have been developed. The amphiphilic beta-CD were formed by anthraquinone (AQ) and cyclodextrins with disulfide bond in between. The disulfide bond is in charge of the responsiveness, while the AQ moiety serves as fluorescent probe. The tumor targeting was introduced by the host-guest inclusion complex between beta-CD and folate (FA), due to the known folate-receptor mediated endocytosis. The responsive disintegration of this beta-CD-AQ-FA micelles and coinstantaneous drug releases happened with cleavage of disulfide bond following tumor targeting and cell endocytosis, which was triggered by massive glutathione in the cytoplasm of tumor cells. The highly selective particle uptake by tumor cells and subsequent efficient drug delivery to these cells, which were directly demonstrated by fluorescence microscopy, resulted in an over twofold efficacy against tumor cells compared with normal cells, as well as higher tumor cytotoxicity than that caused by free drugs. These results indicate that these beta-CD-AQ-FA micelles, with performance of selective drug delivery, responsive drug release, effective drug tracking and tumor labeling, could be a promising platform for better therapeutic effects in cancer treatment.

DOI: 10.1166/jbn.2018.2573