M2 Macrophage Hybrid Membrane-Camouflaged Targeted Biomimetic Nanosomes to Reprogram Inflammatory Microenvironment for Enhanced Enzyme-Thermo-Immunotherapy

作者全名："Chen, Ran; Yang, Jie; Wu, Mingjun; Zhao, Dezhang; Yuan, Ziyi; Zeng, Linggao; Hu, Juan; Zhang, Xinping; Wang, Tingting; Xu, Jingxin; Zhang, Jingqing"

作者地址："[Chen, Ran; Yang, Jie; Zhao, Dezhang; Yuan, Ziyi; Zhang, Xinping; Xu, Jingxin; Zhang, Jingqing] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Wu, Mingjun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Zeng, Linggao] Chongqing Inst Food & Drug Control, NMPA Key Lab Qual Monitoring Narcot Drugs & Psycho, Chongqing 401121, Peoples R China; [Wang, Tingting] Chongqing Med Univ, Expt Teaching & Management Ctr, Biochem & Mol Biol Lab, Chongqing 400016, Peoples R China"

通信作者："Zhang, JQ (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China."

来源：ADVANCED MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001038738300001

JCR分区：Q1

影响因子：27.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：enzyme-thermo-immunotherapy; gouty arthritis; hybrid membrane of M2 macrophage and erythrocyte; inflammatory microenvironment; self-cascade bioenzyme; nanoenzyme

摘要："Excessive inflammatory reactions caused by uric acid deposition are the key factor leading to gout. However, clinical medications cannot simultaneously remove uric acid and eliminate inflammation. An M2 macrophage-erythrocyte hybrid membrane-camouflaged biomimetic nanosized liposome (USM[H]L) is engineered to deliver targeted self-cascading bienzymes and immunomodulators to reprogram the inflammatory microenvironment in gouty rats. The cell-membrane-coating endow nanosomes with good immune escape and lysosomal escape to achieve long circulation time and intracellular retention times. After being uptaken by inflammatory cells, synergistic enzyme-thermo-immunotherapies are achieved: uricase and nanozyme degraded uric acid and hydrogen peroxide, respectively; bienzymes improved the catalytic abilities of each other; nanozyme produced photothermal effects; and methotrexate has immunomodulatory and anti-inflammatory effects. The uric acid levels markedly decrease, and ankle swelling and claw curling are effectively alleviated. The levels of inflammatory cytokines and ROS decrease, while the anti-inflammatory cytokine levels increase. Proinflammatory M1 macrophages are reprogrammed to the anti-inflammatory M2 phenotype. Notably, the IgG and IgM levels in USM[H]L-treated rats decrease substantially, while uricase-treated rats show high immunogenicity. Proteomic analysis show that there are 898 downregulated and 725 upregulated differentially expressed proteins in USM[H]L-treated rats. The protein-protein interaction network indicates that the signaling pathways include the spliceosome, ribosome, purine metabolism, etc."

基金机构："Chongqing Science and Technology Committee [CSTB2022NSCQ-LZX0057]; Chongqing Education Committee [cqmudstd202216, yjg213055, NPKF-2021-02]; CQMU Program for Youth Innovation in Future Medicine [202024]; Foundation for Distinguished Professor of Chongqing Medical University [CSTB2022NSCQ-LZX0057]; NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances; [W0153]"

基金资助正文："& nbsp;R.C., J.Y., and M.W. contributed equally to this work. This research was supported by grants from Chongqing Science and Technology Committee and Chongqing Education Committee (CSTB2022NSCQ-LZX0057), Chongqing Education Committee (cqmudstd202216, yjg213055), NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances (NPKF-2021-02), CQMU Program for Youth Innovation in Future Medicine (W0153), Foundation for Distinguished Professor of Chongqing Medical University (202024). All animal experimental procedures were performed according to the relevant guidelines, and set and regulated by CQMU Animal Care and Use Committee."