Mn-Based Artificial Mitochondrial Complex "VI" Acts as an Electron and Free Radical Conversion Factory to Suppress Macrophage Inflammatory Response

作者全名："Ren, Mingxing; Zhou, Chongjing; Li, Xinyi; Zhang, Yining; Li, Meng; Song, Haoyue; Liu, Fengyi; Chen, Tao; Xu, Xinxin; Yang, Sheng"

作者地址："[Ren, Mingxing; Li, Xinyi; Zhang, Yining; Li, Meng; Song, Haoyue; Liu, Fengyi; Chen, Tao; Xu, Xinxin; Yang, Sheng] Chongqing Med Univ, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China; [Zhou, Chongjing] Chongqing City Hosp Tradit Chinese Med, Dept Stomatol, Chongqing 400021, Peoples R China"

通信作者："Yang, S (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China."

来源：ADVANCED HEALTHCARE MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001160523600001

JCR分区：Q1

影响因子：10

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：bionic mitochondrial complex; ETC regulation; immunomodulation; macrophages; nanozymes

摘要："Disturbance in the mitochondrial electron transport chain (ETC) is a key factor in the emerging discovery of immune cell activation in inflammatory diseases, yet specific regulation of ETC homeostasis is extremely challenging. In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial ""VI"" complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO2 polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H2O2. By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF-kappa B signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation-induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases. An innovative mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial ""VI"" complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis. By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF-kappa B signaling pathway, MCBN effectively suppresses macrophage inflammatory response. image"

基金机构："National Natural Science Foundation of China; Natural Science Foundation of Chongqing [cstc2021jcyj-jqX0028]; Project of Chongqing Medical University Graduate Tutor Team [cqmudstd202203]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0079]; [82171010]"

基金资助正文："M.R. and C.Z. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (Grant No. 82171010), the Natural Science Foundation of Chongqing (Grant NO. cstc2021jcyj-jqX0028), Project of Chongqing Medical University Graduate Tutor Team (cqmudstd202203), the Program for Youth Innovation in Future Medicine, Chongqing Medical University (NO. W0079)."