Jingru Zhao , Jinming Cai , Jinyan Hu , Zhenlin Zhang , Yuan-Yuan Liu , Dengyu Pan , Longxiang Shen , Bijiang Geng
{"title":"具有胆固醇消耗能力的碳点修饰的可生物降解中空二氧化锰用于级联扩增超声免疫治疗","authors":"Jingru Zhao , Jinming Cai , Jinyan Hu , Zhenlin Zhang , Yuan-Yuan Liu , Dengyu Pan , Longxiang Shen , Bijiang Geng","doi":"10.1016/j.biomaterials.2025.123559","DOIUrl":null,"url":null,"abstract":"<div><div>For the effective activation of the adaptive immune response, it is crucial to promote the maturation of dendritic cells (DCs) and subsequently initiate cytotoxic T lymphocytes. Nevertheless, the immunosuppressive tumor microenvironments (TME) are believed to hinder DC maturation, leading to a significant decrease in the effectiveness of immunotherapy. In this work, we present the first instance of combining ROS-triggered immunogenic cell death (ICD), cholesterol depletion, and STING activation to achieve the cascade amplification of antitumor immune response. The Zr-based metal-organic frameworks (MOF) is utilized as the template for the synthesis of hollow MnO<sub>2</sub> (H–MnO<sub>2</sub>). Carbon dots (CDs) with cholesterol depletion capability are then deposited on H–MnO<sub>2</sub> to form heterojunctions. CD@H–MnO<sub>2</sub> not only has improved ROS generation ability under ultrasound due to heterojunction construction, but also shows GSH-responsive degradation properties, enabling the targeted release of CDs and Mn ions in tumors. CD@H–MnO<sub>2</sub>-triggered cascade amplification of antitumor immune response is elucidated as follows: (1) Heterojunction construction, GSH depletion, and relief of hypoxia co-augmented ROS yield could significantly induce a robust ICD effect. (2) The released Mn ions stimulate DC maturation by activating the cGAS-STING pathway. (3) Direct enhancement of T cell toxicity can be realized by CDs through depleting cholesterol. Notable antitumor effects have been observed to eliminate primary tumors and stop the growth of distant tumors. This study presents a novel method to merge ROS-triggered ICD, cholesterol depletion, and STING activation into one nanomaterial to produce long-lasting and powerful immune responses.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"325 ","pages":"Article 123559"},"PeriodicalIF":12.8000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biodegradable hollow MnO2 decorated by carbon dots with cholesterol depletion capability for cascaded amplification of sono-immunotherapy\",\"authors\":\"Jingru Zhao , Jinming Cai , Jinyan Hu , Zhenlin Zhang , Yuan-Yuan Liu , Dengyu Pan , Longxiang Shen , Bijiang Geng\",\"doi\":\"10.1016/j.biomaterials.2025.123559\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>For the effective activation of the adaptive immune response, it is crucial to promote the maturation of dendritic cells (DCs) and subsequently initiate cytotoxic T lymphocytes. Nevertheless, the immunosuppressive tumor microenvironments (TME) are believed to hinder DC maturation, leading to a significant decrease in the effectiveness of immunotherapy. In this work, we present the first instance of combining ROS-triggered immunogenic cell death (ICD), cholesterol depletion, and STING activation to achieve the cascade amplification of antitumor immune response. The Zr-based metal-organic frameworks (MOF) is utilized as the template for the synthesis of hollow MnO<sub>2</sub> (H–MnO<sub>2</sub>). Carbon dots (CDs) with cholesterol depletion capability are then deposited on H–MnO<sub>2</sub> to form heterojunctions. CD@H–MnO<sub>2</sub> not only has improved ROS generation ability under ultrasound due to heterojunction construction, but also shows GSH-responsive degradation properties, enabling the targeted release of CDs and Mn ions in tumors. CD@H–MnO<sub>2</sub>-triggered cascade amplification of antitumor immune response is elucidated as follows: (1) Heterojunction construction, GSH depletion, and relief of hypoxia co-augmented ROS yield could significantly induce a robust ICD effect. (2) The released Mn ions stimulate DC maturation by activating the cGAS-STING pathway. (3) Direct enhancement of T cell toxicity can be realized by CDs through depleting cholesterol. Notable antitumor effects have been observed to eliminate primary tumors and stop the growth of distant tumors. This study presents a novel method to merge ROS-triggered ICD, cholesterol depletion, and STING activation into one nanomaterial to produce long-lasting and powerful immune responses.</div></div>\",\"PeriodicalId\":254,\"journal\":{\"name\":\"Biomaterials\",\"volume\":\"325 \",\"pages\":\"Article 123559\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomaterials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0142961225004788\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0142961225004788","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Biodegradable hollow MnO2 decorated by carbon dots with cholesterol depletion capability for cascaded amplification of sono-immunotherapy
For the effective activation of the adaptive immune response, it is crucial to promote the maturation of dendritic cells (DCs) and subsequently initiate cytotoxic T lymphocytes. Nevertheless, the immunosuppressive tumor microenvironments (TME) are believed to hinder DC maturation, leading to a significant decrease in the effectiveness of immunotherapy. In this work, we present the first instance of combining ROS-triggered immunogenic cell death (ICD), cholesterol depletion, and STING activation to achieve the cascade amplification of antitumor immune response. The Zr-based metal-organic frameworks (MOF) is utilized as the template for the synthesis of hollow MnO2 (H–MnO2). Carbon dots (CDs) with cholesterol depletion capability are then deposited on H–MnO2 to form heterojunctions. CD@H–MnO2 not only has improved ROS generation ability under ultrasound due to heterojunction construction, but also shows GSH-responsive degradation properties, enabling the targeted release of CDs and Mn ions in tumors. CD@H–MnO2-triggered cascade amplification of antitumor immune response is elucidated as follows: (1) Heterojunction construction, GSH depletion, and relief of hypoxia co-augmented ROS yield could significantly induce a robust ICD effect. (2) The released Mn ions stimulate DC maturation by activating the cGAS-STING pathway. (3) Direct enhancement of T cell toxicity can be realized by CDs through depleting cholesterol. Notable antitumor effects have been observed to eliminate primary tumors and stop the growth of distant tumors. This study presents a novel method to merge ROS-triggered ICD, cholesterol depletion, and STING activation into one nanomaterial to produce long-lasting and powerful immune responses.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.