{"title":"以线粒体和厌氧糖酵解为靶向的自组装复合铜纳米粒子促进杯突免疫疗法","authors":"Hanyu Zhang, Jing Xia, Lingling Xie, Meng Hao, Wenlong Liang, Sizhang Wang, Xiao Dong, Yongxin Li, Qiang Mu","doi":"10.1007/s42114-024-01138-4","DOIUrl":null,"url":null,"abstract":"<div><p>Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing the specific accumulation of copper ions in mitochondria while simultaneously enhancing mitochondrial respiration is highly needed and still a major challenge to promote cuproptosis. Herein, the lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with the copper ionophore elesclomol (ES) through copper ion-driven cooperative coordination to form GF/CuES hybrid nanoparticles, synergistically targeting mitochondria and anaerobic glycolysis to boost cuproptosis-immunotherapy. After cellular internalization, the GF/CuES hybrid nanoparticles responsively dissociate to release Cu<sup>2+</sup> and ES, co-transporting into mitochondria to collaboratively trigger cuproptosis, which subsequently evokes immunogenic cell death (ICD). Notably, the liberated GF leads to effective LDH suppression, which not only further amplifies cuproptosis via disrupting anaerobic glycolysis and enhancing mitochondrial respiration but also reduces lactate production, thus alleviating the immunosuppressive tumor microenvironment and augmenting anti-tumor immunity driven by ICD. Thus, the GF/CuES hybrid nanoparticles exhibit strong antitumor effects through cooperatively targeting glycolysis, cuproptosis, and immunotherapy, offering a unique opportunity to enhance cancer treatment strategies.</p></div>","PeriodicalId":7220,"journal":{"name":"Advanced Composites and Hybrid Materials","volume":"8 1","pages":""},"PeriodicalIF":23.2000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondria- and anaerobic glycolysis-targeted self-assembled copper complex nanoparticles for boosting cuproptosis-immunotherapy\",\"authors\":\"Hanyu Zhang, Jing Xia, Lingling Xie, Meng Hao, Wenlong Liang, Sizhang Wang, Xiao Dong, Yongxin Li, Qiang Mu\",\"doi\":\"10.1007/s42114-024-01138-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing the specific accumulation of copper ions in mitochondria while simultaneously enhancing mitochondrial respiration is highly needed and still a major challenge to promote cuproptosis. Herein, the lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with the copper ionophore elesclomol (ES) through copper ion-driven cooperative coordination to form GF/CuES hybrid nanoparticles, synergistically targeting mitochondria and anaerobic glycolysis to boost cuproptosis-immunotherapy. After cellular internalization, the GF/CuES hybrid nanoparticles responsively dissociate to release Cu<sup>2+</sup> and ES, co-transporting into mitochondria to collaboratively trigger cuproptosis, which subsequently evokes immunogenic cell death (ICD). Notably, the liberated GF leads to effective LDH suppression, which not only further amplifies cuproptosis via disrupting anaerobic glycolysis and enhancing mitochondrial respiration but also reduces lactate production, thus alleviating the immunosuppressive tumor microenvironment and augmenting anti-tumor immunity driven by ICD. Thus, the GF/CuES hybrid nanoparticles exhibit strong antitumor effects through cooperatively targeting glycolysis, cuproptosis, and immunotherapy, offering a unique opportunity to enhance cancer treatment strategies.</p></div>\",\"PeriodicalId\":7220,\"journal\":{\"name\":\"Advanced Composites and Hybrid Materials\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":23.2000,\"publicationDate\":\"2024-12-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Composites and Hybrid Materials\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s42114-024-01138-4\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, COMPOSITES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Composites and Hybrid Materials","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s42114-024-01138-4","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, COMPOSITES","Score":null,"Total":0}
Mitochondria- and anaerobic glycolysis-targeted self-assembled copper complex nanoparticles for boosting cuproptosis-immunotherapy
Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing the specific accumulation of copper ions in mitochondria while simultaneously enhancing mitochondrial respiration is highly needed and still a major challenge to promote cuproptosis. Herein, the lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with the copper ionophore elesclomol (ES) through copper ion-driven cooperative coordination to form GF/CuES hybrid nanoparticles, synergistically targeting mitochondria and anaerobic glycolysis to boost cuproptosis-immunotherapy. After cellular internalization, the GF/CuES hybrid nanoparticles responsively dissociate to release Cu2+ and ES, co-transporting into mitochondria to collaboratively trigger cuproptosis, which subsequently evokes immunogenic cell death (ICD). Notably, the liberated GF leads to effective LDH suppression, which not only further amplifies cuproptosis via disrupting anaerobic glycolysis and enhancing mitochondrial respiration but also reduces lactate production, thus alleviating the immunosuppressive tumor microenvironment and augmenting anti-tumor immunity driven by ICD. Thus, the GF/CuES hybrid nanoparticles exhibit strong antitumor effects through cooperatively targeting glycolysis, cuproptosis, and immunotherapy, offering a unique opportunity to enhance cancer treatment strategies.
期刊介绍:
Advanced Composites and Hybrid Materials is a leading international journal that promotes interdisciplinary collaboration among materials scientists, engineers, chemists, biologists, and physicists working on composites, including nanocomposites. Our aim is to facilitate rapid scientific communication in this field.
The journal publishes high-quality research on various aspects of composite materials, including materials design, surface and interface science/engineering, manufacturing, structure control, property design, device fabrication, and other applications. We also welcome simulation and modeling studies that are relevant to composites. Additionally, papers focusing on the relationship between fillers and the matrix are of particular interest.
Our scope includes polymer, metal, and ceramic matrices, with a special emphasis on reviews and meta-analyses related to materials selection. We cover a wide range of topics, including transport properties, strategies for controlling interfaces and composition distribution, bottom-up assembly of nanocomposites, highly porous and high-density composites, electronic structure design, materials synergisms, and thermoelectric materials.
Advanced Composites and Hybrid Materials follows a rigorous single-blind peer-review process to ensure the quality and integrity of the published work.