Combination therapy with ultrasound and 2D nanomaterials promotes recovery after spinal cord injury via Piezo1 downregulation

Feng Zhang; Xiaolie He; Kun Dong; Li Yang; Bei Ma; Yuchen Liu; Zhibo Liu; Bairu Chen; Rongrong Zhu; Liming Cheng

doi:10.1186/s12951-023-01853-y

Combination therapy with ultrasound and 2D nanomaterials promotes recovery after spinal cord injury via Piezo1 downregulation

J Nanobiotechnology. 2023 Mar 15;21(1):91. doi: 10.1186/s12951-023-01853-y.

Authors

Feng Zhang^#^{1

2}, Xiaolie He^#^{1

2

3}, Kun Dong^{1

2

3}, Li Yang^{1

2

3}, Bei Ma^{1

2}, Yuchen Liu^{1

2}, Zhibo Liu^{1

2}, Bairu Chen^{1

2}, Rongrong Zhu^{4

5

6}, Liming Cheng^{7

8

9}

Affiliations

¹ Department of Orthopaedics, School of Medicine, Tongji Hospital Affiliated to Tongji University, Tongji University, Shanghai, 200065, China.
² Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China.
³ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200065, China.
⁴ Department of Orthopaedics, School of Medicine, Tongji Hospital Affiliated to Tongji University, Tongji University, Shanghai, 200065, China. rrzhu@tongji.edu.cn.
⁵ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China. rrzhu@tongji.edu.cn.
⁶ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200065, China. rrzhu@tongji.edu.cn.
⁷ Department of Orthopaedics, School of Medicine, Tongji Hospital Affiliated to Tongji University, Tongji University, Shanghai, 200065, China. limingcheng@tongji.edu.cn.
⁸ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China. limingcheng@tongji.edu.cn.
⁹ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200065, China. limingcheng@tongji.edu.cn.

^# Contributed equally.

Abstract

Spinal cord injury (SCI) causes severe neurological dysfunction and currently has no effective treatment. Due to the complex pathophysiological processes associated with SCI and the limited efficacy of single strategies, the need for combined strategies for effective SCI therapy is becoming increasingly apparent. In this study, we evaluated the combined effects of layered double hydroxide-coupled NT3 (MgFe-LDH/NT3) nanoparticles (NPs) and ultrasound (US) both in vitro and in vivo. Combined treatment promoted neural stem cell (NSC) differentiation into neurons and exerted anti-inflammatory effects in vitro. Furthermore, combined therapy promoted behavioural and electrophysiological performance at eight weeks in a completely transected murine thoracic SCI model. Additional RNA sequencing revealed that ultrasonic-induced Piezo1 downregulation is the core mechanism by which combined therapy promotes neurogenesis and inhibits inflammation, and the Piezo1/NF-κB pathways were identified. Hence, the findings of this study demonstrated that the combination of ultrasound and functional NPs may be a promising novel strategy for repairing SCI.

Keywords: Inflammation; Nanoparticles; Piezo1; Spinal cord injury; Ultrasound.

MeSH terms

Animals
Down-Regulation
Ion Channels / pharmacology
Mice
Nanostructures*
Neural Stem Cells*
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries* / drug therapy

Substances

Piezo1 protein, mouse
Ion Channels

Abstract

MeSH terms

Substances

Grants and funding