{"title":"基于氧合和免疫增强效应的掺铜叶酸碳点/二氧化锰复合物的抗结肠癌活性","authors":"Mingyang Liu, Qing Xia, Xiaodan Wu, Siran Jin, Yutian Xie, Rui Yan*, Yingxue Jin* and Zhiqiang Wang*, ","doi":"10.1021/acs.bioconjchem.4c00184","DOIUrl":null,"url":null,"abstract":"<p >In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO<sub>2</sub>@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO<sub>2</sub>@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. <i>In vivo</i> treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO<sub>2</sub>-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-Colon Cancer Activity of Copper-Doped Folate Carbon Dots/MnO2 Complexes Based on Oxygenation and Immune-Enhancing Effects\",\"authors\":\"Mingyang Liu, Qing Xia, Xiaodan Wu, Siran Jin, Yutian Xie, Rui Yan*, Yingxue Jin* and Zhiqiang Wang*, \",\"doi\":\"10.1021/acs.bioconjchem.4c00184\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO<sub>2</sub>@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO<sub>2</sub>@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. <i>In vivo</i> treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO<sub>2</sub>-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.</p>\",\"PeriodicalId\":29,\"journal\":{\"name\":\"Bioconjugate Chemistry Bioconjugate\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioconjugate Chemistry Bioconjugate\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.bioconjchem.4c00184\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioconjugate Chemistry Bioconjugate","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.bioconjchem.4c00184","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Anti-Colon Cancer Activity of Copper-Doped Folate Carbon Dots/MnO2 Complexes Based on Oxygenation and Immune-Enhancing Effects
In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.
期刊介绍:
Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.