Liang Hongshan, Zhou Bin, He Yun, Pei Yaqiong, Li Bin, Li Jing
College of Food Science and Technology, Huazhong Agricultural University.
Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Ministry of Education.
Int J Nanomedicine. 2017 Apr 26;12:3315-3330. doi: 10.2147/IJN.S130859. eCollection 2017.
In this study, a novel coordination bonding system based on metal-tannic acid (TA) architecture on zein/carboxymethyl chitosan (CMCS) nanoparticles (NPs) was investigated for the pH-responsive drug delivery. CMCS has been reported to coat on zein NPs as delivery vehicles for drugs or nutrients in previous studies. The cleavage of either the "metal-TA" or "NH-metal" coordination bonds resulted in significant release of guest molecules with high stimulus sensitivity, especially in mild acidic conditions. The prepared metal-TA-coated zein/CMCS NPs (zein/CMCS-TA/metal NPs) could maintain particle size in cell culture medium at 37°C, demonstrating good stability compared with zein/CMCS NPs. In vitro release behavior of doxorubicin hydrochloride (DOX)-loaded metal-TA film-coated zein/CMCS NPs (DOX-zein/CMCS-TA/metal NPs) showed fine pH responsiveness tailored by the ratio of zein to CMCS as well as the metal species and feeding concentrations. The blank zein/CMCS-TA/metal NPs (NPs-TA/metal) were of low cytotoxicity, while a high cytotoxic activity of DOX-zein/CMCS-TA/metal NPs (DOX-NPs-TA/metal) against HepG2 cells was demonstrated by in vitro cell assay. Confocal laser scanning microscopy (CLSM) and flow cytometry were combined to study the uptake efficiency of DOX-NPs or DOX-NPs-TA/metal. This system showed significant potential as a highly versatile and potent platform for drug delivery.
在本研究中，研究了一种基于玉米醇溶蛋白/羧甲基壳聚糖（CMCS）纳米颗粒（NPs）上的金属-单宁酸（TA）结构的新型配位键合系统用于pH响应性药物递送。在先前的研究中，已有报道称CMCS可作为药物或营养物质的递送载体包覆在玉米醇溶蛋白NPs上。“金属-TA”或“NH-金属”配位键的断裂会导致客体分子以高刺激敏感性显著释放，尤其是在弱酸性条件下。制备的金属-TA包覆的玉米醇溶蛋白/CMCS NPs（玉米醇溶蛋白/CMCS-TA/金属 NPs）在37°C的细胞培养基中可保持粒径，与玉米醇溶蛋白/CMCS NPs相比显示出良好的稳定性。载有盐酸多柔比星（DOX）的金属-TA薄膜包覆的玉米醇溶蛋白/CMCS NPs（DOX-玉米醇溶蛋白/CMCS-TA/金属 NPs）的体外释放行为表明其pH响应性良好，可通过玉米醇溶蛋白与CMCS的比例以及金属种类和进料浓度进行调节。空白玉米醇溶蛋白/CMCS-TA/金属 NPs（NPs-TA/金属）的细胞毒性较低，而体外细胞试验表明DOX-玉米醇溶蛋白/CMCS-TA/金属 NPs（DOX-NPs-TA/金属）对HepG2细胞具有高细胞毒性活性。结合共聚焦激光扫描显微镜（CLSM）和流式细胞术研究DOX-NPs或DOX-NPs-TA/金属的摄取效率。该系统作为一种高度通用且有效的药物递送平台显示出巨大潜力。
