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基于 CaCO3 矿化的金属-有机骨架的二氢青蒿素程序释放用于协同癌症治疗。

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO Mineralized Metal-Organic Framework.

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan, 250014, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14134-14139. doi: 10.1002/anie.201907388. Epub 2019 Aug 28.

Abstract

Dihydroartemisinin (DHA) has attracted increasing attention as an anticancer agent. However, using DHA to treat cancer usually depends on the synergistic effects of exogenous components, and the loss of DHA during delivery reduces its effectiveness in cancer therapy. Reported herein is a programmed release nanoplatform of DHA to synergistically treat cancer with a Fe-TCPP [(4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid)] NMOF (nanoscale MOF) having a CaCO mineralized coating, which prevents DHA leakage during transport in the bloodstream. When the nanoplatform arrives at the tumor site, the weakly acidic microenvironment and high concentration of glutathione (GSH) trigger DHA release and TCPP activation, enabling the synergistic Fe -DHA-mediated chemodynamic therapy, Ca -DHA-mediated oncosis therapy, and TCPP-mediated photodynamic therapy. In vivo experiments demonstrated that the nanoplatform showed enhanced anticancer efficiency and negligible toxicity.

摘要

二氢青蒿素(DHA)作为一种抗癌药物引起了越来越多的关注。然而,使用 DHA 治疗癌症通常依赖于外源性成分的协同作用,并且在输送过程中 DHA 的损失降低了其在癌症治疗中的功效。本文报道了一种具有 CaCO 矿化涂层的 DHA 程序释放纳米平台,与具有 Fe-TCPP[(4,4,4,4-(卟啉-5,10,15,20-四羧酸)四(苯甲酸)]NMOF(纳米级 MOF)协同治疗癌症,可防止DHA 在血液中运输过程中的泄漏。当纳米平台到达肿瘤部位时,弱酸性微环境和高浓度谷胱甘肽(GSH)触发 DHA 释放和 TCPP 激活,从而实现协同的 Fe-DHA 介导的化学动力学治疗、Ca-DHA 介导的肿瘤坏死治疗和 TCPP 介导的光动力治疗。体内实验表明,该纳米平台表现出增强的抗癌效率和可忽略不计的毒性。

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