MOF nanoparticles with encapsulated dihydroartemisinin as a controlled drug delivery system for enhanced cancer therapy and mechanism analysis
MOF nanoparticles with encapsulated dihydroartemisinin as a controlled drug delivery system for enhanced cancer therapy and mechanism analysis
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具有封装双氢青蒿素的 MOF 纳米颗粒作为受控药物递送系统，用于增强癌症治疗和机制分析
DOI：
10.1039/d0tb01330g
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发表时间：
2020-09-07
影响因子：
7
通讯作者：
Zhu, Wenhe
中科院分区：
文献类型：
--
作者：
Li, Yawei;Song, Yu;Zhu, Wenhe
双氢青蒿素（DHA）作为一种新兴的肿瘤治疗剂越来越受到人们的关注。然而，由于其固有的溶解度低、选择性差、清除快等特性，严重限制了DHA的临床应用。在此，我们报告了一种基于使用沸石咪唑酸框架-8加载DHA的简单而有效的策略（DHA@ZIF-8）。制备的DHA@ZIF-8纳米颗粒在肿瘤酸性微环境中具有较高的药物包封率（77.2%）、良好的稳定性、良好的生物相容性和可控的药物释放。DHA@ZIF-8与游离DHA相比，NPs在vitroandin体内治疗实验中表现出更强的抗肿瘤作用，副作用可以忽略不计。此外，通过RNA测序（RNA-seq）和生物信息学分析，研究了DHA@ZIF-8 NPs的抗肿瘤机制。结果表明DHA@ZIF-8 NPs可修饰HepG2细胞中7090基因的表达，其机制可能与通过p53介导的线粒体途径诱导细胞凋亡和通过抑制PI3K/AKT途径抑制糖酵解有关。本研究强调了利用mof作为一个安全稳定的平台开发高效的给药系统在癌症治疗中的潜力，研究其抗肿瘤机制可以为DHA的临床应用提供理论支持。
Dihydroartemisinin (DHA) has attracted increasing attention as an emerging therapeutic agent for tumor treatment. However, the clinical application of DHA is seriously limited owing to its inherent properties, including low solubility, poor selectivity, and fast clearance. Herein, we report a facile yet efficient strategy based on using zeolitic imidazolate framework-8 to load DHA (DHA@ZIF-8). The as-prepared DHA@ZIF-8 nanoparticles (NPs) possess high drug encapsulation efficiency (77.2%), favorable stability, good biocompatibility and controllable drug release in tumor acidic microenvironments. DHA@ZIF-8 NPs exhibit enhanced antitumor effects compared with free DHA inin vitroandin vivotherapy experiments, accompanied with negligible side effects. Furthermore, the antitumor mechanism of DHA@ZIF-8 NPs is well investigated by RNA sequencing (RNA-seq) and bioinformatics analysis. The results indicate that DHA@ZIF-8 NPs modify the expression of 7090 genes in HepG2 cells, and the mechanism may be related to the induction of apoptosis through a p53-mediated mitochondrial pathway and the suppression of glycolysis by inhibiting the PI3K/AKT pathway. This work highlights the potential of utilizing MOFs as a safe and stable platform for developing a highly efficient drug delivery system in cancer therapy, and the investigation of the antitumor mechanism can provide theoretical support for the clinical usage of DHA.