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MOF-801 作为一种纳米多孔水基载体系统,用于原位封装和持续释放 5-FU,以实现有效的癌症治疗。

MOF-801 as a Nanoporous Water-Based Carrier System for In Situ Encapsulation and Sustained Release of 5-FU for Effective Cancer Therapy.

机构信息

School of Chemistry, College of Science, University of Tehran, Tehran 14155-6455, Iran.

出版信息

Inorg Chem. 2022 Apr 18;61(15):5912-5925. doi: 10.1021/acs.inorgchem.2c00380. Epub 2022 Apr 4.

Abstract

Nanoporous metal-organic frameworks (MOFs) have been gaining a reputation for their drug delivery applications. In the current work, MOF-801 was successfully prepared by a facile, cost-efficient, and environmentally friendly approach through the reaction of ZrCl and fumaric acid as organic linkers to deliver 5-fluorouracil (5-FU). The prepared nanostructure was fully characterized by a series of analytical techniques including Fourier transform infrared spectroscopy, powder X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, UV-vis spectroscopy, H NMR spectroscopy, thermogravimetric analysis, high-performance liquid chromatography, and Brunauer-Emmett-Teller analysis. MOF-801 could be used for the delivery of the anticancer drug 5-FU due to its high surface area, suitable pore size, and biocompatible ingredients. Based on in vitro loading and release studies, a high 5-FU loading capacity and pH-dependent drug release behavior were observed. Moreover, the interactions between the structure of MOFs and 5-FU were investigated through Monte Carlo simulation calculations. An in vitro cytotoxicity test was done, and the results indicated that 5-FU@MOF-801 was more potent than 5-FU on SW480 cancerous cells, indicating the highlighted role of this drug delivery system. Finally, the kinetics of drug release was investigated.

摘要

纳米多孔金属-有机骨架(MOFs)因其在药物传递方面的应用而备受关注。在本工作中,通过 ZrCl 和富马酸作为有机连接物的反应,成功地以简便、经济高效且环保的方法制备了 MOF-801,用于传递 5-氟尿嘧啶(5-FU)。通过一系列分析技术,包括傅里叶变换红外光谱、粉末 X 射线衍射、场发射扫描电子显微镜、能谱分析、紫外-可见光谱、氢核磁共振光谱、热重分析、高效液相色谱和 Brunauer-Emmett-Teller 分析,对制备的纳米结构进行了全面的表征。由于 MOF-801 具有高表面积、合适的孔径和生物相容性成分,因此可用于传递抗癌药物 5-FU。基于体外负载和释放研究,观察到 5-FU 的高负载能力和 pH 依赖性药物释放行为。此外,通过蒙特卡罗模拟计算研究了 MOFs 的结构与 5-FU 之间的相互作用。进行了体外细胞毒性试验,结果表明 5-FU@MOF-801 对 SW480 癌细胞的活性强于 5-FU,表明该药物传递系统具有重要作用。最后,研究了药物释放的动力学。

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