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

Nano Research 2023年第2期16卷 2938-2948页

作者： Xiaoru Sun Huitong Ruan Qidong Liu Silu Cao Qi Jing Yaru Xu Lize Xiong Wenguo Cui Cheng Li Department of Anesthesiology and Perioperative Medicine Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Shanghai 200434China

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

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