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Research Article

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

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.

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Graphical Abstract

Inspired by the inflammation of neurodegenerative disease microenvironment, a “nanobiosignaler” system was constructed by modifying the nanoparticles with microglia-targeted peptide to deliver the biosignal factor for specifically regulating microglia polarization, thereby inhibiting neuroinflammation.

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

biosignalnanoparticlesmicroglianeuroinflammationtargeted delivery

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Nano Research
Volume 16 Issue 2,
February 2023
Pages 2938-2948
DOI: 10.1007/s12274-022-5143-3
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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Received: 25 August 2022
Revised: 01 October 2022
Accepted: 02 October 2022
Published: 25 November 2022
© Tsinghua University Press 2022
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