{"title":"多通道免疫纳米调节剂抑制乳酸代谢和乳酸形状的酸性微环境,根治抗肿瘤免疫抑制。","authors":"Chao Fang,Qiuxia Peng,Xiaoying Li,Xiao Qu,Zi Qiao,Binxu Yin,Lujia Xiao,Yi Chen,Xiulin Dong,Lulu Cai,Litao Sun,Kun Zhang","doi":"10.1002/adma.202512230","DOIUrl":null,"url":null,"abstract":"Lactic acid (LA) itself and the LA-shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non-inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)-modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO2 and load R848, respectively, followed by liposome coating, anti-CD105 modification and FC-mediated O2 binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO2 delivery. Ultrasound-triggered FC-binding O2 burst and liposomes-destruction-enhanced CaO2 reactions with H+ and H2O produce O2. This process depletes pre-existing H+ and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non-inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti-tumor efficacy of cancer calcification and intratumoral H2O2 accumulation in the immune nanoregulators especially after anti-CD105-mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non-inflammatory macrophages-induced cancer immunosuppression.","PeriodicalId":114,"journal":{"name":"Advanced Materials","volume":"91 1","pages":"e12230"},"PeriodicalIF":26.8000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multichannel Immune Nanoregulators Suppress Lactic Acid Metabolism and Lactic Acid-Shaped Acidic Microenvironment to Uproot Anti-Tumor Immunosuppression.\",\"authors\":\"Chao Fang,Qiuxia Peng,Xiaoying Li,Xiao Qu,Zi Qiao,Binxu Yin,Lujia Xiao,Yi Chen,Xiulin Dong,Lulu Cai,Litao Sun,Kun Zhang\",\"doi\":\"10.1002/adma.202512230\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Lactic acid (LA) itself and the LA-shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non-inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)-modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO2 and load R848, respectively, followed by liposome coating, anti-CD105 modification and FC-mediated O2 binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO2 delivery. Ultrasound-triggered FC-binding O2 burst and liposomes-destruction-enhanced CaO2 reactions with H+ and H2O produce O2. This process depletes pre-existing H+ and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non-inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti-tumor efficacy of cancer calcification and intratumoral H2O2 accumulation in the immune nanoregulators especially after anti-CD105-mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non-inflammatory macrophages-induced cancer immunosuppression.\",\"PeriodicalId\":114,\"journal\":{\"name\":\"Advanced Materials\",\"volume\":\"91 1\",\"pages\":\"e12230\"},\"PeriodicalIF\":26.8000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Materials\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1002/adma.202512230\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/adma.202512230","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Multichannel Immune Nanoregulators Suppress Lactic Acid Metabolism and Lactic Acid-Shaped Acidic Microenvironment to Uproot Anti-Tumor Immunosuppression.
Lactic acid (LA) itself and the LA-shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non-inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)-modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO2 and load R848, respectively, followed by liposome coating, anti-CD105 modification and FC-mediated O2 binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO2 delivery. Ultrasound-triggered FC-binding O2 burst and liposomes-destruction-enhanced CaO2 reactions with H+ and H2O produce O2. This process depletes pre-existing H+ and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non-inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti-tumor efficacy of cancer calcification and intratumoral H2O2 accumulation in the immune nanoregulators especially after anti-CD105-mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non-inflammatory macrophages-induced cancer immunosuppression.
期刊介绍:
Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.