Journal of the American Chemical Society, Vol.135, No.28, 10542-10549, 2013
pH-Responsive Supramolecular Vesicles Based on Water-Soluble Pillararene and Ferrocene Derivative for Drug Delivery
The drug delivery system based on supramolecular vesicles that were self-assembled by a novel host-guest inclusion complex between a water-soluble pillararene (WP6) and hydrophobic ferrocene derivative in water has been developed. The inclusion complexation between WP6 and ferrocene derivative in water was studied by H-1 NMR, UV-vis, and fluorescence spectroscopy, which showed a high binding constant of (1.27 +/- 0.42) x 10(5) M-1 with 1:1 binding stoichiometry. This resulting inclusion complex could self-assemble into supramolecular vesicles that displayed a significant pH-responsive behavior in aqueous solution, which were investigated by fluorescent probe technique, dynamic laser scattering, and transmission electron microscopy. Furthermore, the drug loading and in vitro drug release studies demonstrated that these supramolecular vesicles were able to encapsulate mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which particularly showed rapid MTZ release at low-pH environment. More importantly, the cellular uptake of these pH-responsive MTZ-loaded vesicles by cancer cells was observed by living cell imaging techniques, and their cytotoxicity assay indicated that unloaded vesicles had low toxicity to normal cells, which could dramatically reduce the toxicity of MTZ upon loading of MTZ. Meanwhile, MTZ-loaded vesicles exhibited comparable anticancer activity in vitro as free MTZ to cancer cells under examined conditions. This study suggests that such supramolecular vesicles have great potential as controlled drug delivery systems.