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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.

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Publication history
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Acknowledgements

Publication history

Received: 25 August 2022
Revised: 01 October 2022
Accepted: 02 October 2022
Published: 25 November 2022
Issue date: February 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

The present study was 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 SY-XKZT-2021-2001), and Natural Science Foundation of Shanghai (No. 16ZR1426400).

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