Atmosphere-inspired multilayered nanoarmor with modulable protection and delivery of Interleukin-4 for inflammatory microenvironment modulation

作者全名："Ge, Xin; Hu, Junfeng; Peng, Yuan; Zeng, Zhuo; He, Danfeng; Li, Xilan; Chen, Yajie; Luo, Gaoxing; Deng, Jun; Xu, Zhigang; He, Song"

作者地址："[Ge, Xin; He, Song] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China; [Hu, Junfeng; Xu, Zhigang] Southwest Univ, Minist Educ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Chongqing 400715, Peoples R China; [Hu, Junfeng; Xu, Zhigang] Southwest Univ, Chongqing Engn Res Ctr Micronano Biomed Mat & Devi, Chongqing 400715, Peoples R China; [Peng, Yuan] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Plast & Reconstruct Surg, Shanghai 200011, Peoples R China; [Peng, Yuan; Zeng, Zhuo; He, Danfeng; Li, Xilan; Chen, Yajie; Luo, Gaoxing; Deng, Jun] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Inst Burn Res,State Key Lab Trauma Burn & Combined, Chongqing 400038, Peoples R China"

通信作者："He, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China.; Xu, ZG (通讯作者)，Southwest Univ, Minist Educ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Chongqing 400715, Peoples R China.; Xu, ZG (通讯作者)，Southwest Univ, Chongqing Engn Res Ctr Micronano Biomed Mat & Devi, Chongqing 400715, Peoples R China.; Luo, GX; Deng, J (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Inst Burn Res,State Key Lab Trauma Burn & Combined, Chongqing 400038, Peoples R China."

来源：BIOMATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001051263600001

JCR分区：Q1

影响因子：12.8

年份：2023

卷号：301

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Nanoarmor; Inflammatory bowel disease; Immunoregulation; Macrophage polarization

摘要："Inflammatory bowel disease (IBD) has been closely associated with immune disorders and excessive M1 macrophage activation, which can be reversed by the M2-polarizing effect of interleukin-4 (IL-4). However, maintaining native IL-4 activity with its specific release in the inflammatory microenvironment and efficient biological performance remain a challenge. Inspired by the multilayered defense mechanism of the earth's atmosphere, we constructed a multilayered protective nanoarmor (NA) for IL-4 delivery (termed as IL-4@PEGRA NAs) into an intricate inflammatory microenvironment. The poly(ethylene glycol) (PEG)-ylated phenolic rosmarinic acid (RA)-grafted copolymer contains two protective layers-the intermediate polyphenol (RA molecules) and outermost shield (PEG) layers-to protect the biological activity of IL-4 and prolong its circulation in blood. Moreover, IL-4@PEGRA NAs scavenge reactive oxygen species with the specific release of IL-4 and maximize its biofunction at the site of inflammation, leading to M2 macrophage polarization and downregulation of inflammatory mediators. Simultaneously, gut microbiota dysbiosis can improve to amplify the M2-polarizing effect and inhibit the phosphatidylinositol 3 kinase/Akt signaling pathway, thereby attenuating inflammation and promoting colitis tissue repair. It provides a nature-inspired strategy for constructing an advanced multilayered NA delivery system with protective characteristics and potential for IBD management."

基金机构："National Natural Science Foundation of China [82222039, 82102323, 82202447]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0775]; Chongqing Talents of Exceptional Young Talents Project, China [cstc2021ycjh-bgzxm0061]; State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University [SKLKF202208]; Key project for clinical innovation of Army Medical University [CX2019LC107]"

基金资助正文："X.G., J.H., and Y.P. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (82222039, 82102323, 82202447) , the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0775) , Chongqing Talents of Exceptional Young Talents Project, China (No. cstc2021ycjh-bgzxm0061) , the State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University (Grant No. SKLKF202208) , and Key project for clinical innovation of Army Medical University (CX2019LC107) ."