氧化铈团簇酶仿生合成及其对急性肝损伤治疗的研究

doi:10.15541/jim20250086

无机材料学报 ›› 2026, Vol. 41 ›› Issue (2): 245-252.DOI: 10.15541/jim20250086 CSTR: 32189.14.10.15541/jim20250086

氧化铈团簇酶仿生合成及其对急性肝损伤治疗的研究

严弥迦¹^,²(), 张佳乐¹^,², 张秋红¹(), 陈航榕¹^,²

1.国科大杭州高等研究院, 化学与材料科学学院, 杭州 310024
2.中国科学院上海硅酸盐研究所, 上海 200050

收稿日期:2025-02-26 修回日期:2025-03-21 出版日期:2025-06-10 网络出版日期:2025-06-10
通讯作者: 张秋红, 副研究员. E-mail: zhangqh@ucas.ac.cn
作者简介:严弥迦(1999-), 女, 硕士研究生. E-mail: yanmijia22@mails.ucas.ac.cn
基金资助:
国科大杭州高等研究院科研基金(B03006C01600407);国科大杭州高等研究院科研基金(A05006C019014);关键陶瓷材料全国重点实验室开放课题(SKL202412SIC)

CeO₂ Clusterzymes: Biomimetic Synthesis and Treatment for Acute Liver Injury

YAN Mijia¹^,²(), ZHANG Jiale¹^,², ZHANG Qiuhong¹(), CHEN Hangrong¹^,²

1. School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
2. Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China

Received:2025-02-26 Revised:2025-03-21 Published:2025-06-10 Online:2025-06-10
Contact: ZHANG Qiuhong, associate professor. E-mail: zhangqh@ucas.ac.cn
About author:YAN Mijia (1999-), female, Master candidate. E-mail: yanmijia22@mails.ucas.ac.cn
Supported by:
Research Funds of Hangzhou Institute for Advanced Study, UCAS(B03006C01600407);Research Funds of Hangzhou Institute for Advanced Study, UCAS(A05006C019014);Opening Project of State Key Laboratory of Advanced Ceramics(SKL202412SIC)

摘要/Abstract

摘要：

对乙酰氨基酚(Acetaminophen, APAP)过量服用是临床上急性肝损伤(Acute Liver Injury, ALI)的常见诱因, 主要病理特征为大量活性氧(Reactive Oxygen Species, ROS)累积和炎性细胞浸润。本研究通过仿生矿化工艺制备了一种超小尺寸(约1.3 nm)氧化铈团簇酶(CeO₂ Clusterzymes, CeCs), 该材料具有高的氧空位含量(52.6%)和高的Ce³⁺/Ce⁴⁺比例(1.06), 对多种ROS(包括自由基)具有优异的吸附和清除能力, 可用于肝细胞保护。动物体内实验进一步证实CeCs可以实现APAP诱导的ALI的高效干预治疗, 显著延长治疗窗口和逆转无菌炎症, 表现出潜在的临床应用价值。

关键词: 氧化铈, 团簇酶, 急性肝损伤, 抗氧化, 抗炎

Abstract:

Acetaminophen (APAP) overdose is a common cause of acute liver injury (ALI) in clinical settings, characterized by accumulation of reactive oxygen species (ROS) and infiltration of inflammatory cells. In this study, CeO₂clusterzymes (named as CeCs) with ultra-small size (around 1.3 nm) was synthesized by a biomimetic mineralization process. The obtained CeCs presented a high oxygen vacancy content (52.6%) and a high Ce³⁺/Ce⁴⁺ ratio (1.06), showing excellent adsorption and removal abilities to various ROS (including free radicals), which could be used for hepatocyte protection. In vivo animal experiments further confirmed that CeCs provided highly effective therapeutic intervention for APAP-induced ALI, extending the therapeutic window, and reversing sterile inflammation, underscoring their potential for clinical application.

Key words: cerium oxide, clusterzyme, acute liver injury, antioxidant, anti-inflammatory

中图分类号:

R318

严弥迦, 张佳乐, 张秋红, 陈航榕. 氧化铈团簇酶仿生合成及其对急性肝损伤治疗的研究[J]. 无机材料学报, 2026, 41(2): 245-252.

YAN Mijia, ZHANG Jiale, ZHANG Qiuhong, CHEN Hangrong. CeO₂ Clusterzymes: Biomimetic Synthesis and Treatment for Acute Liver Injury[J]. Journal of Inorganic Materials, 2026, 41(2): 245-252.

图/表 6

图1 CeCs和CeNPs的理化性能表征

Fig. 1 Physical and chemical properties of CeCs and CeNPs (a) TEM images of CeCs; (b) Hydrodynamic size of CeCs and CeNPs; (c) Zeta potential of CeCs and CeNPs; (d) XPS total spectrum of CeCs; (e, f) High resolution XPS spectra on Ce3d (e) and O1s (f) of CeCs; (g) XPS total spectrum of CeNPs; (h, i) High resolution XPS spectra on Ce3d (h) and O1s (i) of CeNPs

图2 CeCs和CeNPs对多种ROS的清除能力

Fig. 2 Scavenging capability of CeCs and CeNPs to various ROS (a)·OH; (b) H2O2; (c) ABTS·. Corlorful figures are available on website

图3 细胞内抗氧化活性与肝细胞保护

Fig. 3 Intracellular antioxidant activity and hepatocytes protection (a) Cytotoxicity profiles of different concentrations of CeCs on BNL CL.2 cells; (b) Protective effect of different concentrations of CeCs on APAP-treated cells; (c) Fluorescence images of generation of ROS by APAP-treated cells incubated with different samples APAP: Acetaminophen

图4 不同浓度CeCs和CeNPs的溶血实验评价

Fig. 4 Evaluation of hemolysis performance of CeCs and CeNPs at different concentrations

图5 APAP诱导急性肝损伤小鼠的治疗效果评价

Fig. 5 Evaluation of therapeutic effect of APAP-induced acute liver injury mice (a, b) Serum levels of ALT and AST in APAP-induced acute liver injury BALB/c mice in 2 (a) and 6 h (b) treatment groups; (c, d) Serum levels of ALT and AST in APAP-induced acute liver injury C57BL/6 mice in 2 (c) and 6 h (d) treatment groups APAP: Acetaminophen; ALT: Glutamate aminotransferase; AST: Aspartate aminotransferase

图6 APAP诱导急性肝损伤小鼠的抗炎效果评价

Fig. 6 Evaluation of anti-inflammatory effect of APAP-induced ALI mice (a, b) Flow cytometry to determine expression of Ly-6G (neutrophil markers), CD86 (M1 phenotypic macrophage markers) and CD206 (M2 phenotypic macrophage markers) on liver tissues after different treatment; (c) Quantification of neutrophils; (d) M1 macrophages; (e) M2 macrophages; (f) M1/M2 ratio APAP: Acetaminophen; ALI: Acute liver injury

参考文献 33

[1]	STRAVITZ R T, LEE W M. Acute liver failure. The Lancet, 2019, 394(10201): 869. DOI URL
[2]	FERNÁNDEZ J, BASSEGODA O, TOAPANTA D, et al. Acute liver failure: a practical update. JHEP Reports, 2024, 6(9): 101131. DOI URL
[3]	BERNAL W, WENDON J. Acute liver failure. New England Journal of Medicine, 2013, 369(26): 2525. DOI URL
[4]	DU K, RAMACHANDRAN A, JAESCHKE H. Oxidative stress during acetaminophen hepatotoxicity: sources, pathophysiological role and therapeutic potential. Redox Biology, 2016, 10: 148. DOI PMID
[5]	WANG F, YUAN H, SHEN J, et al. Nanozymes with broad-spectrum scavenging of reactive oxygen species (ROS) alleviate inflammation in acute liver injury. ACS Materials Letters, 2024, 6(4): 1304. DOI URL
[6]	AHMED O, ROBINSON M W, O’FARRELLY C. Inflammatory processes in the liver: divergent roles in homeostasis and pathology. Cellular & Molecular Immunology, 2021, 18(6): 1375.
[7]	LIU J, HAN X, ZHANG T, et al. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy. Journal of Hematology & Oncology, 2023, 16(1): 100124.
[8]	TENÓRIO M C D S, GRACILIANO N G, MOURA F A, et al. N-acetylcysteine (NAC): impacts on human health. Antioxidants, 2021, 10(6): 967. DOI URL
[9]	LI F, QIU Y, XIA F, et al. Dual detoxification and inflammatory regulation by ceria nanozymes for drug-induced liver injury therapy. Nano Today, 2020, 35: 100925.
[10]	YANG R, MIKI K, HE X, et al. Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity. Critical Care, 2009, 13(2): R55.
[11]	MUHAMMAD F, HUANG F, CHENG Y, et al. Nanoceria as an electron reservoir: spontaneous deposition of metal nanoparticles on oxides and their anti-inflammatory activities. ACS Nano, 2022, 16(12): 20567. DOI PMID
[12]	KOO S, SOHN H S, KIM T H, et al. Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model. Nature Nanotechnology, 2023, 18(12): 1502. DOI PMID
[13]	IM G B, KIM Y G, YOO T Y, et al. Ceria nanoparticles as copper chaperones that activate SOD1 for synergistic antioxidant therapy to treat ischemic vascular diseases. Advanced Materials, 2023, 35(16): 2208989. DOI URL
[14]	WANG L, ZHU B, DENG Y, et al. Biocatalytic and antioxidant nanostructures for ROS scavenging and biotherapeutics. Advanced Functional Materials, 2021, 31(31): 2101804. DOI URL
[15]	KIM Y G, LEE Y, LEE N, et al. Ceria-based therapeutic antioxidants for biomedical applications. Advanced Materials, 2023, 36(10): 2210819. DOI URL
[16]	YUN L X, WU H, SHEN Z G, et al. Ultrasmall CeO₂ nanoparticles with rich oxygen defects as novel catalysts for efficient glycolysis of polyethylene terephthalate. ACS Sustainable Chemistry & Engineering, 2022, 10(16): 5278.
[17]	梁云燕, 孙芳营, 尚利. 基于金纳米团簇类酶活性的比色传感研究. 分析化学, 2021, 49(6): 931.
[18]	SUN S, LIU H, XIN Q, et al. Atomic engineering of clusterzyme for relieving acute neuroinflammation through lattice expansion. Nano Letters, 2021, 21(6): 2562. DOI PMID
[19]	FU S, CHEN H, YANG W, et al. ROS-targeted depression therapy via BSA-incubated ceria nanoclusters. Nano Letters, 2022, 22(11): 4519. DOI URL
[20]	WANG Y, WU Y, LIU Y, et al. BSA-mediated synthesis of bismuth sulfide nanotheranostic agents for tumor multimodal imaging and thermoradiotherapy. Advanced Functional Materials, 2016, 26(29): 5335. DOI URL
[21]	BLANCO E, SHEN H, FERRARI M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 2015, 33(9): 941. DOI PMID
[22]	SUN Y, LU D, ZHANG H, et al. Titanium oxide electrocatalytic membrane filtration: “two faces” of oxygen vacancies in generation and transformation of reactive oxygen species. Environmental Science & Technology, 2023, 57(35): 13226. DOI URL
[23]	KESAVARDHANA S, MALIREDDI R K S, KANNEGANTI T. Caspases in cell death, inflammation, and pyroptosis. Annual Review of Immunology, 2020, 38(1): 567. DOI PMID
[24]	BHUSHAN B, APTE U. Liver regeneration after acetaminophen hepatotoxicity. The American Journal of Pathology, 2019, 189(4): 719. DOI URL
[25]	ZHAO C, LI Z, CHEN J, et al. Site-specific biomimicry of antioxidative melanin formation and its application for acute liver injury therapy and imaging. Advanced Materials, 2021, 33(34): 2102391. DOI URL
[26]	ROTUNDO L, PYRSOPOULOS N. Liver injury induced by paracetamol and challenges associated with intentional and unintentional use. World Journal of Hepatology, 2020, 12(4): 125. DOI PMID
[27]	郑惠星.对乙酰氨基酚诱导小鼠急性肝损伤模型机理研究. 延吉: 延边大学硕士学位论文, 2015.
[28]	ETEMADI Y, AKAKPO J Y, RAMACHANDRAN A, et al. Nrf2 as a therapeutic target in acetaminophen hepatotoxicity: a case study with sulforaphane. Journal of Biochemical and Molecular Toxicology, 2023, 37(12): e23505. DOI URL
[29]	KANG D, KIM C K, JEONG H, et al. Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage. Nano Research, 2017, 10(8): 2743. DOI URL
[30]	于慧杰, 盛国光. 三种品系小鼠对伴刀豆球蛋白A所致急性肝损伤的耐受性比较研究. 实用肝脏病杂志, 2014, 17(2): 168.
[31]	SHAN X, LI J, LIU J, et al. Targeting ferroptosis by poly(acrylic) acid coated Mn₃O₄ nanoparticles alleviates acute liver injury. Nature Communications, 2023, 14: 7598. DOI
[32]	XIA F, HU X, ZHANG B, et al. Ultrasmall ruthenium nanoparticles with boosted antioxidant activity upregulate regulatory T cells for highly efficient liver injury therapy. Small, 2022, 18(29): 2201558. DOI URL
[33]	MU J, LI C, SHI Y, et al. Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia- reperfusion injury. Nature Communications, 2022, 13: 2513. DOI

氧化铈团簇酶仿生合成及其对急性肝损伤治疗的研究

CeO₂ Clusterzymes: Biomimetic Synthesis and Treatment for Acute Liver Injury

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 33

相关文章 15

编辑推荐

Metrics

本文评价

[1]	马新超, 智清, 李威, 陈毛, 王海龙, 张锐, 张帆, 范冰冰. Fe₂AlB₂的高温氧化机制及吸波性能研究[J]. 无机材料学报, 2026, 41(1): 45-54.
[2]	柴润宇, 张镇, 王孟龙, 夏长荣. 直接组装法制备氧化铈基金属支撑固体氧化物燃料电池[J]. 无机材料学报, 2025, 40(7): 765-771.
[3]	李筱暄, 付前刚, 文子豪, 杨金山, 倪德伟, 张洁, 程源, 刘昱轩, 褚衍辉, 蔡飞燕, 王京阳, 张幸红. 极端环境用超高温陶瓷结构材料研究进展[J]. 无机材料学报, 2025, 40(10): 1045-1078.
[4]	王文婷, 徐敬军, 马科, 李美栓, 李兴超, 李同起. 原位反应/热压合成Ti₂AlC-20TiB₂复合材料在1000~1300 ℃空气中的高温氧化行为[J]. 无机材料学报, 2025, 40(1): 31-38.
[5]	蔡飞燕, 倪德伟, 董绍明. 高熵碳化物超高温陶瓷的研究进展[J]. 无机材料学报, 2024, 39(6): 591-608.
[6]	刘国昂, 王海龙, 方成, 黄飞龙, 杨欢. B₄C含量对(Ti_0.25Zr_0.25Hf_0.25Ta_0.25)B₂-B₄C陶瓷力学性能及抗氧化性能的影响[J]. 无机材料学报, 2024, 39(6): 697-706.
[7]	郑斌, 康凯, 张青, 叶昉, 解静, 贾研, 孙国栋, 成来飞. 前驱体转化陶瓷法制备Ti₃SiC₂陶瓷及其热稳定性研究[J]. 无机材料学报, 2024, 39(6): 733-740.
[8]	张幸红, 王义铭, 程源, 董顺, 胡平. 超高温陶瓷复合材料研究进展[J]. 无机材料学报, 2024, 39(6): 571-590.
[9]	周云凯, 刁亚琪, 王明磊, 张宴会, 王利民. 聚苯胺改性Ti₃C₂(OH)₂抗氧化性的第一性原理计算研究[J]. 无机材料学报, 2024, 39(10): 1151-1158.
[10]	舒朝琴, 朱敏, 朱钰方. 熔盐法制备含钴氯磷灰石及其抗氧化性能和细胞相容性研究[J]. 无机材料学报, 2022, 37(11): 1225-1235.
[11]	王皓轩, 刘巧沐, 王一光. 高熵过渡金属碳化物陶瓷的研究进展[J]. 无机材料学报, 2021, 36(4): 355-364.
[12]	张亚晨, 孟佳, 蔡坤, 盛晓晨, 乐军, 宋力昕. 基于声发射技术的Si-Cr-Ti高温抗氧化涂层弯曲失效机理研究[J]. 无机材料学报, 2021, 36(11): 1185-1192.
[13]	黄秀兵, 王鹏, 陶进长, 席作帅. CeO₂修饰Mn-Fe-O复合材料及其NH₃-SCR脱硝催化性能[J]. 无机材料学报, 2020, 35(5): 573-580.
[14]	余汉青, 董志军, 袁观明, 丛野, 李轩科, 罗永明. B-C掺杂SiC纤维的制备及其性能研究[J]. 无机材料学报, 2019, 34(5): 493-501.
[15]	杨志宾, 岳彤联, 余向南, 吴苗苗. 钴掺杂氧化铈纳米粒子电催化性能研究[J]. 无机材料学报, 2018, 33(8): 845-853.

氧化铈团簇酶仿生合成及其对急性肝损伤治疗的研究

CeO2 Clusterzymes: Biomimetic Synthesis and Treatment for Acute Liver Injury

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 33

相关文章 15

编辑推荐

Metrics

本文评价

CeO₂ Clusterzymes: Biomimetic Synthesis and Treatment for Acute Liver Injury