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  3. An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain

  • ACS Nano. 2024 Jan 18. doi: 10.1021/acsnano.3c08097.
Wenbo Yang 1,  Kanglu Li 1,  Qing Pan 1,  Wei Huang 1,  Yan Xiao 2,  Hui Lin 1,  Sheng Liu 1,  Xuanzuo Chen 1,  Xiao Lv 1,  Shiqing Feng 3 4 5,  Zengwu Shao 1,  Xiangcheng Qing 1,  Yizhong Peng 1
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
  • 2 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
  • 3 The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People's Republic of China.
  • 4 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin Medical University, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin 300052, People's Republic of China.
  • 5 Department of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.
PMID: 38237054 DOI: 10.1021/acsnano.3c08097
Abstract

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of Reactive Oxygen Species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, Apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC Apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced Calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

Keywords

ROS scavenger; biomembrane-coated nanoparticles; cytokine trap; disc degeneration; discogenic pain.

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