{"title":"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。","authors":"Xiaohuan Guo, Qi Fang, Nan Leng, Yuan Liu, Bingbing Cai, Yuzhu Zhou, Changchun Wen","doi":"10.1088/1748-605X/ad82c7","DOIUrl":null,"url":null,"abstract":"<p><p>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 H<sub>2</sub>O<sub>2</sub>deficiency 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), Cu<sup>2+</sup>, and Mn<sup>2+</sup>were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H<sub>2</sub>O<sub>2</sub>in the presence of oxygen to increase the H<sub>2</sub>O<sub>2</sub>content in tumors, Cu<sup>2+</sup>reduces GSH content and generates Cu<sup>+</sup>in the tumor, and Cu<sup>+</sup>and Mn<sup>2+</sup>catalyze H<sub>2</sub>O<sub>2</sub>to 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 growth<i>in vivo</i>, indicating a good CDT effect.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyaluronic acid modified Cu/Mn-doped metal-organic framework nanocatalyst for chemodynamic therapy.\",\"authors\":\"Xiaohuan Guo, Qi Fang, Nan Leng, Yuan Liu, Bingbing Cai, Yuzhu Zhou, Changchun Wen\",\"doi\":\"10.1088/1748-605X/ad82c7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 H<sub>2</sub>O<sub>2</sub>deficiency 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), Cu<sup>2+</sup>, and Mn<sup>2+</sup>were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H<sub>2</sub>O<sub>2</sub>in the presence of oxygen to increase the H<sub>2</sub>O<sub>2</sub>content in tumors, Cu<sup>2+</sup>reduces GSH content and generates Cu<sup>+</sup>in the tumor, and Cu<sup>+</sup>and Mn<sup>2+</sup>catalyze H<sub>2</sub>O<sub>2</sub>to 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 growth<i>in vivo</i>, indicating a good CDT effect.</p>\",\"PeriodicalId\":72389,\"journal\":{\"name\":\"Biomedical materials (Bristol, England)\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical materials (Bristol, England)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1088/1748-605X/ad82c7\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical materials (Bristol, England)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1088/1748-605X/ad82c7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.