用于化学动力疗法的透明质酸修饰铜/锰掺杂金属有机框架纳米催化剂。

Xiaohuan Guo, Qi Fang, Nan Leng, Yuan Liu, Bingbing Cai, Yuzhu Zhou, Changchun Wen
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摘要

化学动力疗法(CDT)是一种新的癌症治疗方法,它能在肿瘤微环境中产生高毒性活性氧(ROS),诱导癌细胞凋亡或坏死。然而,细胞内 H2O2 的缺乏和谷胱甘肽等抗氧化剂的活性往往会阻碍 CDT 的治疗效果。本研究利用自组装铜/锰掺杂金属有机框架开发了一种纳米催化剂 HCM,并用透明质酸修饰其表面,从而构建了一种具有更高的效率和特异性的肿瘤靶向 CDT 治疗剂。研究表明,HHTP(2, 3, 6, 7, 10, 11- hexahydroxybenzophenanthrene)、Cu2+和Mn2+三种物质在弱酸性条件下可在肿瘤细胞中分解释放。HHTP 在有氧的情况下会产生外源 H2O2,从而增加肿瘤中的 H2O2 含量;Cu2+ 会降低谷胱甘肽的含量,并在肿瘤中生成 Cu+;Cu+ 和 Mn2+ 会催化 H2O2,从而在类似芬顿的反应中产生 ∙OH。这三个因素共同改变了肿瘤微环境,提高了 ROS 生成的效率。HCM 对癌细胞具有选择性和高效的细胞毒性,并能有效抑制肿瘤在体内的生长,具有良好的 CDT 效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hyaluronic acid modified Cu/Mn-doped metal-organic framework nanocatalyst for chemodynamic therapy.

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular H2O2deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu2+, and Mn2+were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H2O2in the presence of oxygen to increase the H2O2content in tumors, Cu2+reduces GSH content and generates Cu+in the tumor, and Cu+and Mn2+catalyze H2O2to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growthin vivo, indicating a good CDT effect.

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