Engineered macrophage-biomimetic versatile nanoantidotes for inflammation-targeted therapy against Alzheimer’s disease by neurotoxin neutralization and immune recognition suppression

作     者：Meng Cheng Caihua Ye Chunxiao Tian Dongju Zhao Haonan Li Zuhao Sun Yuyang Miao Qiang Zhang Junping Wang Yan Dou 

作者机构：Department of Radiology and Tianjin Key Laboratory of Functional ImagingTianjin Medical University General HospitalTianjin300052PR China School of Biomedical Engineering and TechnologyTianjin Medical UniversityTianjin300070PR China School of Life SciencesTianjin UniversityTianjin300072PR China Department of GeriatricsTianjin Medical University General HospitalTianjin Geriatrics InstituteTianjin300052PR China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第26卷第8期

页      面：337-352页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100203[医学-老年医学] 10[医学] 

基　　金：financially supported by the National Natural Science Foundation of China(Grant No.81871431,82171905 and 81801828) the Tianjin Natural Science Foundation(Grant No.21JCQNJC01570 and 22JCYBJC01340) Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-001A) Tianjin Municipal Education Research Project(20140115) Fund for Distinguished Young Scholars of Tianjin Medical University General Hospital(22ZYYJQ03). 

主　　题：Alzheimer’s disease Biomimetic nanomedicine Biological neutralization Immune recognition and response Neuroinflammation-targeted therapy 9.4T MR imaging 

摘      要：Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.