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

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Bioactive Materials 2023年第8期26卷 337-352页

作者： Meng Cheng Caihua Ye Chunxiao Tian Dongju Zhao Haonan Li Zuhao Sun Yuyang Miao Qiang Zhang Junping Wang Yan Dou Department of Radiology and Tianjin Key Laboratory of Functional Imaging Tianjin Medical University General HospitalTianjin300052PR China School of Biomedical Engineering and Technology Tianjin Medical UniversityTianjin300070PR China School of Life Sciences Tianjin UniversityTianjin300072PR China Department of Geriatrics Tianjin Medical University General HospitalTianjin Geriatrics InstituteTianjin300052PR China

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.

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

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Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics

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Bioactive Materials 2023年第5期23卷 80-100页

作者： Wanli Song Pengfei Jia Yaping Ren Junmiao Xue Bingqian Zhou Xinkai Xu Yansheng Shan Jing Deng Qihui Zhou Department of Stomatology Institute for Translational MedicineThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266003China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325000China Dental Biomaterials Technology Innovation Center of Qingdao Qingdao266003ShandongChina School of Stomatology Qingdao UniversityQingdao266003China Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid Tianjin300038China School of Rehabilitation Sciences and Engineering University of Health and Rehabilitation SciencesQingdao266071China

White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,Biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.

关键词： White blood cell membrane-camouflaged nanocarriers Inflammation targeting Biological neutralization Immune modulation

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