TALENT EDUCATION

Xi’an Jiaotong University has made a series of new progress in the biomedical application of carbon point nanoenzymes


Nanozymes are a class of nanomaterials with enzymatic properties, capable of catalyzing substrates of enzymes under physiological or extreme conditions, with enzymatic reaction kinetics similar to natural enzymes, and can be used in human health as an alternative to enzymes. Since it was first reported in 2007, 420 research units in 55 countries around the world have successively reported the nanozyme activities of nearly 1200 different nanomaterials, and their catalytic types include oxidoreductases, hydrolases, lyases and isomerases. Nanozymes are a model of multidisciplinary cross-integration and were rated as one of the top ten emerging chemical technologies by IUPAC in 2022. After more than ten years of development, under the joint promotion of scientists engaged in chemistry, enzymology, materials, biology, medicine, theoretical calculation and other fields, nanozymes have become a new research hotspot.
As a class of photoluminescent nanomaterials, carbon dots (C-dots) have received great research attention in the past 10 years because of their unique properties. The carbon dot has the advantages of small particle size, easy preparation and low cost, and its surface is rich in oxygen-containing functional groups, such as carbonyls, carboxyl groups, hydroxyl groups, etc., so that the carbon dots have good water solubility and easy functionalization. Therefore, carbon dots show great application potential in sensing, biological imaging, light-emitting diodes, disease treatment and other aspects. In addition, carbon dots exhibit catalytic activity due to their small size effect and abundant active sites, but previously reported carbon dot nanoenzymes mainly focus on their peroxidase activity, and reports on the design of carbon dot nanoenzymes with high antioxidant activity are rare. The research team designed a carbon dot nanoenzyme (active > 10000 U/mg) with ultra-high SOD-like activity, and revealed its catalytic mechanism by using the surface structure directional regulation strategy and theoretical calculation. The results show that the hydroxyl group and carboxyl group of the carbon point SOD nanoenzyme can combine with the superoxide anion through hydrogen bonding, and the carbonyl group conjugated with the π-system seizes an electron of the superoxide anion to produce oxygen and reduced carbon dots. The reduced carbon dot is oxidized back to its initial state by another superoxide anion and hydrogen peroxide is produced. In vitro experimental results show that carbon dot nanoenzymes can selectively target oxidatively damaged cells and localize to mitochondria, which is very beneficial for removing intracellular ROS from the source. Combined with its high catalytic activity, carbon dot SOD nanoenzymes were successfully applied to resist oxidative stress caused by ischemic stroke in vivo, and achieved good therapeutic effects. In addition, carbon point SOD nanoenzymes have the advantages of high stability, easy preparation, low cost and easy large-scale production, overcome the limitations of natural enzymes, and show great application potential in industry, medicine, biology and other fields.

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Preparation and catalytic mechanism of carbon dot SOD nanoenzymes and their application in the treatment of ischemic stroke
The above research results were published in Nature Communications with the title “Analysis of the catalytic mechanism of carbon point nanoenzyme superoxide dismutase activity”, with Gao Wenhui, School of Basic Medical Sciences, Xi’an Jiaotong University, He Jiuyang and Chen Lei of the Institute of Biophysics, Chinese Academy of Sciences as co-first authors, Yan Xiyun, academician of the Institute of Biophysics, Chinese Academy of Sciences, and researcher Fan Kelong. Professor Pang Daiwen of Nankai University and Associate Professor Liu Cui and Professor Zhang Mingzhen of Xi’an Jiaotong University School of Basic Medicine are the co-corresponding authors of the paper, and the School of Basic Medicine of Xi’an Jiaotong University is the first correspondence unit of the paper.
Link to the paper: https://doi.org/10.1038/s41467-023-35828-2
There is a cascade catalytic reaction in organisms, that is, in the process of chain enzymatic reaction, the product of the previous reaction is the substrate of the latter reaction, and each catalytic reaction makes the regulatory signal amplify. Cascade catalytic reaction systems in organisms ensure accurate signal transduction and efficient metabolism by confineing multiple enzymes to subcellular compartments. By reducing the diffusion barrier, increasing the local concentration of the intermediate and improving the atomic economy of the entire reaction, the advantages over traditional multi-step reactions are obtained. The research group combined highly activated carbon point SOD nanoenzymes (CNDs) with platinum nanoparticles (Pt) to design and develop a Pt@CNDs nanozyme with high-efficiency cascade (SOD-CAT) nanoenzyme activity, which not only solved the problem of oxidative toxicity of carbon point SOD nanoenzyme catalytic product (H2O2), but also converted free radicals into biosafe water and oxygen, exerted cascade amplification catalytic activity, and had excellent effects in living anti-inflammatory.

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Synthesis of Pt@CNDs cascade nanoenzymes and scavenging of reactive oxygen species (ROS)
The above research results were published in Nano Today under the title “Research on Pt@CNDs nanoenzymes with SOD/CAT cascade catalytic activity for antioxidant therapy”, with Yujie Zhang and Wenhui Gao of the School of Basic Medical Sciences of Xi’an Jiaotong University as co-first authors, Tu Kangsheng, researcher in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University, and researcher Zhang Mingzhen and associate professor Liu Cui of the School of Basic Medical Sciences, Xi’an Jiaotong University as co-corresponding authors of the paper. The Department of Hepatobiliary Surgery, Affiliated Hospital of Xi’an Jiaotong University, is the first communication unit of the paper.
Link to paper: https://doi.org/10.1016/j.nantod.2023.101768
The effective combination of the physicochemical properties of nanozymes and the activity of enzymes will provide new ideas for disease treatment. However, how to design nanozymes with good physicochemical properties and enzyme activity is still a major problem in nanoenzymology. The research group developed a novel fluorescent carbon dot (C-dot) superoxide dismutase (SOD) nanoenzyme with a fluorescence emission wavelength of 683 nm, an absolute quantum yield of up to 14%, and showed SOD enzyme activity of more than 4000 U/mg, which provides great potential for biodistribution imaging and treatment of inflammatory diseases in vivo by the nanoenzyme itself. Through surface modification, the researchers revealed that carboxyls, hydroxyl groups, and amino groups on the surface of carbon dots are all closely related to the enzymatic activity of SOD. The carboxyl, hydroxyl, and amino groups on the surface of the carbon dot can all capture superoxide anions by hydrogen bonding. The electron-deficient structure on the surface of the carbon point can seize an electron of the superoxide anion and generate oxygen and reduced carbon dots. Since the large π-system (C=C/C=N) on the carbon dot forms p-π conjugate with its obtained electrons, the intermediate product (reduced carbon dot) is stabilized. Subsequently, another superoxide takes an electron from the reduced carbon dot to produce H2O2, and the structure of the carbon dot is restored. In addition, carbon dot nanoenzymes efficiently enter cells, accumulate in mitochondria, and protect living cells from oxidative damage by removing ROS and reducing levels of pro-inflammatory factors. In vivo experimental results show that carbon dot SOD nanoenzyme has inflammation targeting, and its therapeutic effect on acute lung injury in mice is comparable to that of the clinical drug dexamethasone. These research results will promote the development of ultra-small nanoenzymes with high catalytic activity and good fluorescence performance, and promote their application in the treatment of inflammatory diseases.

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Study on the catalytic mechanism of fluorescent/SOD enzyme activity bifunctional carbon dots and its application in the treatment of acute lung injury
The above research results were published in Advanced Functional Materials under the title “Red fluorescence emitted carbon dot superoxide dismutase nanoenzyme for improving acute lung injury and biological imaging”, Liu Cui, associate professor of the School of Basic Medical Sciences, Xi’an Jiaotong University, and Fan Wenbin, deputy chief physician of the Department of Thoracic Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, as co-first authors of the paper, and Associate Professor Zhu Minrong of Shenzhen University. Researcher Fan Kelong of the Institute of Biophysics, Chinese Academy of Sciences, and Associate Professor Luo Qingying of Shenzhen Key Laboratory of Micro-nano Biosensors are co-corresponding authors of the paper. The School of Basic Medicine of Xi’an Jiaotong University is the first communication unit for papers.
Link to the paper: https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202213856
Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory disease of the intestine, mainly including ulcerative colitis (UC) and Crohn’s disease (CD). UC is confined to the colon, and superficial mucosal inflammation extends proximal continuously, leading to ulceration, haemorrhage, toxic megacolon, and fulminant colitis; CD, on the other hand, can affect any part of the digestive tract, and lesions are usually discontinuous, characterized by transmural inflammation, which can lead to complications such as fibrotic strictures, fistulas, and abscesses. Clinically, the treatment of IBD mainly includes non-targeted therapies (such as aminosalicylates, glucocorticoids, and immunomodulators) and targeted biological therapies (such as anti-TNF preparations). Unfortunately, these drugs are symptomatic and do not cure the disease. Therefore, the development of new technologies and methods for the diagnosis and treatment of IBD will provide an effective basis for its comprehensive prevention and treatment, which has major social needs.
The research group cooperated with the team of Professor Liang Jie of Xijing Hospital of the Fourth Military Medical University to synthesize a multifunctional carbon dot nanomaterial by using glutathione and biotin by hot solvent method. The carbon dot has good SOD enzyme activity, hydroxyl radical scavenging ability and good fluorescence performance. In the IBD model, the nanozyme can not only improve intestinal inflammation, but also can be used for in vivo fluorescence imaging of the intestine. Therefore, this study expands the application of antioxidant nanoenzymes in the treatment of IBD.

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Synthesis of carbon dot nanoenzymes with fluorescence imaging/SOD enzyme activity and its application in the treatment of IBD
The above research results were published in Carbon under the title “Multifunctional carbon dots with superoxide-like dismutase activity and red fluorescence for the treatment of inflammatory bowel disease”, with Ma Yana of the School of Basic Medicine of Xi’an Jiaotong University as the first author of the paper, Professor Liang Jie of Xijing Hospital of the Fourth Military Medical University, Associate Professor Liu Cui and Professor Zhang Mingzhen of the School of Basic Medical Sciences of Xi’an Jiaotong University as the co-corresponding authors of the paper. The School of Basic Medicine of Xi’an Jiaotong University is the first communication unit for papers.
Link to paper: https://doi.org/10.1016/j.carbon.2023.01.006
 
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