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热刺激触发生物相容性多孔金属有机框架释放药物

Thermal Stimuli-Triggered Drug Release from a Biocompatible Porous Metal-Organic Framework.

作者信息

Jiang Ke, Zhang Ling, Hu Quan, Zhang Qi, Lin Wenxin, Cui Yuanjing, Yang Yu, Qian Guodong

机构信息

State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, P. R. China.

Department of Pharmacology, School of Medicine, Hangzhou Normal University, Hangzhou, 310036, P. R. China.

出版信息

Chemistry. 2017 Jul 26;23(42):10215-10221. doi: 10.1002/chem.201701904. Epub 2017 Jul 6.

Abstract

Drug delivery carriers with a high drug loading capacity and biocompatibility, especially for controlled drug release, are urgently needed due to the side effects and frequently dose in the traditional therapeutic method. In our work, a Zr-based metal-organic framework named ZJU-801, which is isoreticular with NU-801, has been designed and further demonstrated as an excellent drug delivery system (DDS) with a high drug loading of 41.7 %. Such a high drug loading capacity may be ascribed to the appropriate match of the size and the large pore volume of this kind of Zr MOF material. Compared with DS@NU-801, this DDS has successfully achieved on-command heating-activated drug release, which was probably attributed to the bulkier ligand, the better stability, and the intense π-π interaction between ZJU-801 and diclofenac sodium (DS) demonstrated comprehensively by SEM, powder X-ray diffraction (PXRD), FTIR and C solid-state NMR spectroscopy as well as computer simulations. It is worth noting that premature drug release was avoided effectively without any complicated post-modifications. The low cytotoxicity and good biocompatibility of our DDS were certificated by the in vitro favorable results from an MTT assay, a WST-1 assay, and confocal microscopy imaging.

摘要

由于传统治疗方法存在副作用且给药频繁,因此迫切需要具有高载药量和生物相容性的药物递送载体,尤其是用于药物控释的载体。在我们的工作中,设计了一种与NU-801同构的基于锆的金属有机框架ZJU-801,并进一步证明其是一种优异的药物递送系统(DDS),载药量高达41.7%。如此高的载药量可能归因于这种锆基金属有机框架材料的尺寸与大孔体积的适当匹配。与DS@NU-801相比,该药物递送系统成功实现了按需加热激活药物释放,这可能归因于体积更大的配体、更好的稳定性以及通过扫描电子显微镜(SEM)、粉末X射线衍射(PXRD)、傅里叶变换红外光谱(FTIR)、碳固体核磁共振波谱(C solid-state NMR spectroscopy)以及计算机模拟全面证明的ZJU-801与双氯芬酸钠(DS)之间强烈的π-π相互作用。值得注意的是,无需任何复杂的后修饰即可有效避免药物过早释放。我们的药物递送系统的低细胞毒性和良好生物相容性通过MTT法、WST-1法和共聚焦显微镜成像的体外良好结果得到了验证。

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