College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, P.R. China.
Sci Rep. 2016 Nov 23;6:37705. doi: 10.1038/srep37705.
An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.
首次设计并制备了一种先进的多功能、中空金属有机骨架(MOF)药物输送系统,该系统具有高载药水平和靶向输送能力,用于抑制肿瘤细胞生长。该中空 MOF 靶向药物输送系统是通过简单的后合成表面改性程序制备的,从首次通过溶剂热条件下温和的相转化成功获得的中空 ZIF-8 开始。结果,中空 ZIF-8 对模型抗癌药物 5-氟尿嘧啶(5-FU)具有更高的载药能力。随后,将负载 5-FU 的 ZIF-8 封装到聚合物层(FA-CHI-5-FAM)中,该聚合物层由三个成分组成:壳聚糖(CHI)骨架、成像剂 5-羧基荧光素(5-FAM)和靶向试剂叶酸(FA)。因此,制备了先进的药物输送系统 ZIF-8/5-FU@FA-CHI-5-FAM。细胞成像实验表明,ZIF-8/5-FU@FA-CHI-5-FAM 可以靶向并被 MGC-803 细胞摄取。此外,正如细胞活力测定所证实的那样,由于 5-FU 的释放,制备的 ZIF-8/5-FU@FA-CHI-5-FAM 对 MGC-803 细胞表现出更强的细胞生长抑制作用。此外,体外药物释放实验表明,ZIF-8/5-FU@FA-CHI-5-FAM 具有高载药能力(51%)和持续的药物释放行为。因此,ZIF-8/5-FU@FA-CHI-5-FAM 可以提供靶向药物运输、成像跟踪和局部持续释放。