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载有大麻二酚的 Mg-没食子酸酯金属有机骨架基潜在治疗脑胶质瘤药物。

A cannabidiol-loaded Mg-gallate metal-organic framework-based potential therapeutic for glioblastomas.

机构信息

Department of Chemistry, University of Delhi, India.

Department of Chemical and Biological Engineering, University at Buffalo, USA.

出版信息

J Mater Chem B. 2021 Mar 17;9(10):2505-2514. doi: 10.1039/d0tb02780d.

DOI:10.1039/d0tb02780d
PMID:33657198
Abstract

Cannabidiol (CBD) has been shown to slow cancer cell growth and is toxic to human glioblastoma cell lines. Thus, CBD could be an effective therapeutic for glioblastoma. In the present study, we explored the anticancer effect of cannabidiol loaded magnesium-gallate (CBD/Mg-GA) metal-organic framework (MOF) using the rat glioma brain cancer (C6) cell line. Bioactive and microporous magnesium gallate MOF was employed for simultaneous delivery of two potential anticancer agents (gallic acid and CBD) to the cancer cells. Gallic acid (GA), a polyphenolic compound, is part of the MOF framework, while CBD is loaded within the framework. Slow degradation of CBD/Mg-GA MOF in physiological fluids leads to sustained release of GA and CBD. CBD's anti-cancer actions target mitochondria, inducing their dysfunction and generation of harmful reactive oxygen species (ROS). Anticancer effects of CBD/Mg-GA include a significant increase in ROS production and a reduction in anti-inflammatory responses as reflected by a significant decrease in TNF-α expression levels. Molecular mechanisms that underlie these effects include the modulation of NF-κB expression, triggering the apoptotic cascades of glioma cells. CBD/Mg-GA MOF has potential anti-cancer, anti-inflammatory and anti-oxidant properties. Thus, the present study demonstrates that CBD/Mg-GA MOF may be a promising therapeutic for glioblastoma.

摘要

大麻二酚 (CBD) 已被证明可减缓癌细胞生长,并且对人神经胶质瘤细胞系有毒。因此,CBD 可能是治疗神经胶质瘤的有效方法。在本研究中,我们使用大鼠神经胶质瘤脑癌 (C6) 细胞系探索了负载大麻二酚的镁没食子酸 (CBD/Mg-GA) 金属有机骨架 (MOF) 的抗癌作用。生物活性和微孔镁没食子酸 MOF 被用于同时将两种潜在的抗癌剂(没食子酸和 CBD)递送到癌细胞中。没食子酸 (GA) 是一种多酚化合物,是 MOF 骨架的一部分,而 CBD 则负载在骨架内。CBD/Mg-GA MOF 在生理流体中的缓慢降解导致 GA 和 CBD 的持续释放。CBD 的抗癌作用针对线粒体,导致其功能障碍和产生有害的活性氧物种 (ROS)。CBD/Mg-GA 的抗癌作用包括 ROS 产生的显著增加和抗炎反应的减少,这反映在 TNF-α 表达水平的显著降低。这些作用的潜在分子机制包括 NF-κB 表达的调节,触发神经胶质瘤细胞的凋亡级联。CBD/Mg-GA MOF 具有潜在的抗癌、抗炎和抗氧化特性。因此,本研究表明 CBD/Mg-GA MOF 可能是治疗神经胶质瘤的一种有前途的方法。

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