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Nano Research 2023, 16(2): 2938-2948 https://doi.org/10.1007/s12274-022-5143-3
Research Article | Issue | Published: 25 November 2022

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

Show Author's Information Xiaoru Sun1,3,4,§,  Huitong Ruan2,§( ),  Qidong Liu1,3,4,  Silu Cao1,3,4,  Qi Jing1,3,4,  Yaru Xu1,3,4,  Lize Xiong1,3,4( ),  Wenguo Cui2( ),  Cheng Li1,3,4( )
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
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
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai 200434, China

§ Xiaoru Sun and Huitong Ruan contributed equally to this work.

Keywords:
microglia, nanoparticles, neuroinflammation, biosignal, targeted delivery
Topics:
Targeted drug delivery
Cite this article:
Sun X, Ruan H, Liu Q, et al. Targeted regulation of neuroinflammation via nanobiosignaler for repairing the central nerve system injuries. Nano Research, 2023, 16(2): 2938-2948. https://doi.org/10.1007/s12274-022-5143-3
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Abstract Full text Electronic supplementary material About this article

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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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Xiaoru Sun1,3,4,§, Huitong Ruan2,§( ), Qidong Liu1,3,4, Silu Cao1,3,4, Qi Jing1,3,4, Yaru Xu1,3,4, Lize Xiong1,3,4( ), Wenguo Cui2( ), Cheng Li1,3,4( )
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
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
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai 200434, China

§ Xiaoru Sun and Huitong Ruan contributed equally to this work.

Abstract

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.

Keywords: microglia, nanoparticles, neuroinflammation, biosignal, targeted delivery

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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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