{"title":"以碳点为支撑的原子分散金作为线粒体氧化应激放大器用于癌症治疗","authors":"Ningqiang Gong, Xiaowei Ma, Xiaoxia Ye, Qunfang Zhou, Xiaoai Chen, Xiaoli Tan, Shengkun Yao, Shuaidong Huo, Tingbin Zhang, Shizhu Chen, Xucong Teng, Xixue Hu, Jie Yu, Yaling Gan, Huaidong Jiang, Jinghong Li, Xing-Jie Liang","doi":"10.1038/s41565-019-0373-6","DOIUrl":null,"url":null,"abstract":"Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications. Atomically dispersed gold supported by carbon dots amplifies mitochondrial oxidative stress, and leads to irreversible cell damage, inhibiting hepatocellular carcinoma in animal models.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":null,"pages":null},"PeriodicalIF":38.1000,"publicationDate":"2019-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41565-019-0373-6","citationCount":"321","resultStr":"{\"title\":\"Carbon-dot-supported atomically dispersed gold as a mitochondrial oxidative stress amplifier for cancer treatment\",\"authors\":\"Ningqiang Gong, Xiaowei Ma, Xiaoxia Ye, Qunfang Zhou, Xiaoai Chen, Xiaoli Tan, Shengkun Yao, Shuaidong Huo, Tingbin Zhang, Shizhu Chen, Xucong Teng, Xixue Hu, Jie Yu, Yaling Gan, Huaidong Jiang, Jinghong Li, Xing-Jie Liang\",\"doi\":\"10.1038/s41565-019-0373-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications. Atomically dispersed gold supported by carbon dots amplifies mitochondrial oxidative stress, and leads to irreversible cell damage, inhibiting hepatocellular carcinoma in animal models.\",\"PeriodicalId\":18915,\"journal\":{\"name\":\"Nature nanotechnology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":38.1000,\"publicationDate\":\"2019-02-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1038/s41565-019-0373-6\",\"citationCount\":\"321\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature nanotechnology\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://www.nature.com/articles/s41565-019-0373-6\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature nanotechnology","FirstCategoryId":"88","ListUrlMain":"https://www.nature.com/articles/s41565-019-0373-6","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Carbon-dot-supported atomically dispersed gold as a mitochondrial oxidative stress amplifier for cancer treatment
Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications. Atomically dispersed gold supported by carbon dots amplifies mitochondrial oxidative stress, and leads to irreversible cell damage, inhibiting hepatocellular carcinoma in animal models.
期刊介绍:
Nature Nanotechnology is a prestigious journal that publishes high-quality papers in various areas of nanoscience and nanotechnology. The journal focuses on the design, characterization, and production of structures, devices, and systems that manipulate and control materials at atomic, molecular, and macromolecular scales. It encompasses both bottom-up and top-down approaches, as well as their combinations.
Furthermore, Nature Nanotechnology fosters the exchange of ideas among researchers from diverse disciplines such as chemistry, physics, material science, biomedical research, engineering, and more. It promotes collaboration at the forefront of this multidisciplinary field. The journal covers a wide range of topics, from fundamental research in physics, chemistry, and biology, including computational work and simulations, to the development of innovative devices and technologies for various industrial sectors such as information technology, medicine, manufacturing, high-performance materials, energy, and environmental technologies. It includes coverage of organic, inorganic, and hybrid materials.