Abstract
The aim of this study was to design a pH- and redox-dual responsive Bletilla striata polysaccharide (BSP)-based copolymer to enhance anti-tumor drugs release at tumor sites and improve the therapeutic effect. The copolymer was synthesized using stearic acid (SA) and cystamine via a disulfide linkage and characterized using 1H-Nuclear Magnetic Resonance spectroscopy and Fourier Transform Infrared spectroscopy. The BSP-ss-SA copolymer could self-assemble into micelle in an aqueous environment and could encapsulate docetaxel therein. Its inhibitory effects on HepG2 cells and 4 T1 cells were determined. Besides, the anti-cancer effects in vivo and histopathological study of 4 T1-bearing tumor mice were also evaluated. Docetaxel-loaded BSP-ss-SA micelles showed significant pH-sensitive release behavior, supplying a greater drug release percentage in pH 5.0 media compared to pH 7.4 media. BSP-ss-SA micelles exhibited a clear redox-responsive release property in pH 7.4 media whereas the similar cumulative release percentage of docetaxel from BSP-ss-SA micelles in pH 5.0 media in the presence and absence of DL-dithiothreitol. The Docetaxel-loaded BSP-ss-SA micelles clearly inhibited the proliferation of HepG2 and 4 T1 cells compared with docetaxel solution. The results of MTT and histopathological study indicated that BSP-ss-SA copolymer exhibited good blood compatibility. The BSP-ss-SA copolymer may be used as carriers to deliver anti-tumor drugs to special tumor tissues.
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