Targeted regulation of neuroinflammation via nanobiosignaler for repairing the central nerve system injuries  

作　　者：Xiaoru Sun Huitong Ruan Qidong Liu Silu Cao Qi Jing Yaru Xu Lize Xiong Wenguo Cui Cheng Li 

机构地区：[1]Department of Anesthesiology and Perioperative Medicine,Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai 200434,China [2]Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Translational Research Institute of Brain and Brain-Like Intelligence,Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai 200434,China [4]Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation,Shanghai 200434,China

出　　处：《Nano Research》2023年第2期2938-2948,共11页纳米研究（英文版）

基　　金：supported by the Found of National Natural Science Foundation of China(Nos.82003658,82101261,81930051,and 82271223);Shanghai Fourth People’s Hospital,School of Medicine,Tongji University(Nos.sykyqd01901 and SYXKZT-2021-2001);Natural Science Foundation of Shanghai(No.16ZR1426400).

摘　　要：Neuroinflammation,commonly associated with various central nervous system(CNS)diseases such as postoperative cognitive dysfunction(POCD),is primarily mediated by the disruption of biological signals in microglia.However,the effective treatment of CNS diseases remains an ongoing challenge as biological signals show limited microglia-targeting effect.In this study,taking advantage of the highly expressed lipoprotein receptor-related protein-1(LRP1)on the microglia,a nanobiosignal delivery system modified by LRP1 high-affinity peptide ligand RAP12(RAP:receptor-associated protein)was constructed to specifically regulate neuroinflammation via targeting microglia.The uptake of the RAP12 modified-nanobiosignaler by microglia increased significantly,indicating its microglia-targeting ability.Both in vitro/vivo studies proved that the“nanobiosignaler”significantly reduced the secretion of pro-inflammatory cytokines,induced specific M2(anti-inflammatory type)microglia differentiation,and remarkably alleviated cognitive function impairment in the mice model when compared with unmodified groups.It was indicated that the“nanobiosignaler”could target microglia to deliver the biological signal and inhibit the excessive activation of microglia.Overall,the cell-targeted biological signal transmission system inspired by“nanobiosignaler”has broad application prospects in the future.

关 键 词：biosignal NANOPARTICLES MICROGLIA NEUROINFLAMMATION targeted delivery 

分 类 号：R741[医药卫生—神经病学与精神病学]