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

炎症 细胞生物学 材料科学 炎症性肠病 促炎细胞因子 免疫学 癌症研究 生物 医学 病理 疾病
作者
Xin Ge,Junfeng Hu,Peng Yuan,Zhuo Zeng,Danfeng He,Xilan Li,Yajie Chen,Gaoxing Luo,Jun Deng,Zhigang Xu,Song He
出处
期刊:Biomaterials [Elsevier BV]
卷期号:301: 122254-122254 被引量:22
标识
DOI:10.1016/j.biomaterials.2023.122254
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.
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