Yanlin Zhu, Xinxin Wang, Lili Feng, Ruoxi Zhao, Can Yu, Yuanli Liu, Ying Xie, Bin Liu, Yang Zhou, Piaoping Yang
{"title":"诱发癌细胞热解和二硫化钼的金属间化合物可促进抗肿瘤免疫力","authors":"Yanlin Zhu, Xinxin Wang, Lili Feng, Ruoxi Zhao, Can Yu, Yuanli Liu, Ying Xie, Bin Liu, Yang Zhou, Piaoping Yang","doi":"10.1038/s41467-024-53135-2","DOIUrl":null,"url":null,"abstract":"<p>Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) and soybean phospholipid (SP) as pyroptosis promoters (Pd<sub>2</sub>Sn@GOx-SP), that not only induce pyroptosis by cascade biocatalysis for remodeling tumor microenvironment and facilitating tumor cell immunogenicity, but also trigger disulfidptosis mediated by cystine accumulation to further promote tumor pyroptosis in female mice. Experiments and density functional theory calculations show that Pd<sub>2</sub>Sn nanorods with an intermediate size exhibit stronger photothermal and enzyme catalytic activity compared with the other three morphologies investigated. The peroxidase-mimic and oxidase-mimic activities of Pd<sub>2</sub>Sn cause potent reactive oxygen species (ROS) storms for triggering pyroptosis, which could be self-reinforced by photothermal effect, hydrogen peroxide supply accompanied by glycometabolism, and oxygen production from catalase-mimic activity of Pd<sub>2</sub>Sn. Moreover, the increase of NADP<sup>+</sup>/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause disulfidptosis and further augment ROS-mediated pyroptosis, respectively. This two-pronged treatment strategy could represent an alternative therapeutic approach to expand anti-tumor immunotherapy.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":null,"pages":null},"PeriodicalIF":14.7000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity\",\"authors\":\"Yanlin Zhu, Xinxin Wang, Lili Feng, Ruoxi Zhao, Can Yu, Yuanli Liu, Ying Xie, Bin Liu, Yang Zhou, Piaoping Yang\",\"doi\":\"10.1038/s41467-024-53135-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) and soybean phospholipid (SP) as pyroptosis promoters (Pd<sub>2</sub>Sn@GOx-SP), that not only induce pyroptosis by cascade biocatalysis for remodeling tumor microenvironment and facilitating tumor cell immunogenicity, but also trigger disulfidptosis mediated by cystine accumulation to further promote tumor pyroptosis in female mice. Experiments and density functional theory calculations show that Pd<sub>2</sub>Sn nanorods with an intermediate size exhibit stronger photothermal and enzyme catalytic activity compared with the other three morphologies investigated. The peroxidase-mimic and oxidase-mimic activities of Pd<sub>2</sub>Sn cause potent reactive oxygen species (ROS) storms for triggering pyroptosis, which could be self-reinforced by photothermal effect, hydrogen peroxide supply accompanied by glycometabolism, and oxygen production from catalase-mimic activity of Pd<sub>2</sub>Sn. Moreover, the increase of NADP<sup>+</sup>/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause disulfidptosis and further augment ROS-mediated pyroptosis, respectively. This two-pronged treatment strategy could represent an alternative therapeutic approach to expand anti-tumor immunotherapy.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.7000,\"publicationDate\":\"2024-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-024-53135-2\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-024-53135-2","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity
Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) and soybean phospholipid (SP) as pyroptosis promoters (Pd2Sn@GOx-SP), that not only induce pyroptosis by cascade biocatalysis for remodeling tumor microenvironment and facilitating tumor cell immunogenicity, but also trigger disulfidptosis mediated by cystine accumulation to further promote tumor pyroptosis in female mice. Experiments and density functional theory calculations show that Pd2Sn nanorods with an intermediate size exhibit stronger photothermal and enzyme catalytic activity compared with the other three morphologies investigated. The peroxidase-mimic and oxidase-mimic activities of Pd2Sn cause potent reactive oxygen species (ROS) storms for triggering pyroptosis, which could be self-reinforced by photothermal effect, hydrogen peroxide supply accompanied by glycometabolism, and oxygen production from catalase-mimic activity of Pd2Sn. Moreover, the increase of NADP+/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause disulfidptosis and further augment ROS-mediated pyroptosis, respectively. This two-pronged treatment strategy could represent an alternative therapeutic approach to expand anti-tumor immunotherapy.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.