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

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 eng...

Full description

Saved in:
Bibliographic Details
Published in:Advanced materials (Weinheim) 2023-09, Vol.35 (39), p.e2304123-e2304123
Main Authors: Chen, Ran, Yang, Jie, Wu, Mingjun, Zhao, Dezhang, Yuan, Ziyi, Zeng, Linggao, Hu, Juan, Zhang, Xinping, Wang, Tingting, Xu, Jingxin, Zhang, Jingqing
Format: Article
Language:English
Subjects:
Biomimetics
Cytokines
Enzymes
Hydrogen peroxide
Immunomodulators
Immunotherapy
Macrophages
Materials science
Membranes
Methotrexate
Proteins
Uric acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.202304123