1. Academic Validation
  2. Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes

Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes

  • Adv Sci (Weinh). 2025 Jan 9:e2412526. doi: 10.1002/advs.202412526.
Ke Wang 1 Judun Zheng 2 Ronghai Li 3 4 Tianjun Chen 1 Yanming Ma 1 Ping Wu 1 Jianxian Luo 1 Jingyi Zhu 5 Weiqiang Lin 6 Minghai Zhao 2 Yue Yuan 3 4 Wen Ma 4 Xiumei Lin 4 7 Yang Wang 4 7 Longqi Liu 3 4 7 Peng Gao 3 8 Hongsheng Lin 1 Chuanyu Liu 3 8 Yuhui Liao 6 Zhisheng Ji 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
  • 2 Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China.
  • 3 BGI Research, Shenzhen, 518083, China.
  • 4 BGI Research, Hangzhou, 310030, China.
  • 5 Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
  • 6 Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
  • 7 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 8 Shanxi Medical University - BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Abstract

Spinal cord injury (SCI) impairs the central nervous system and induces the myelin-sheath-deterioration because of Reactive Oxygen Species (ROS), further hindering the recovery of function. Herein, the simultaneously emergency treatment and dynamic luminescence severity assessment (SETLSA) strategy is designed for SCI based on cerium (Ce)-doped upconversion antioxidant nanoenzymes (Ce@UCNP-BCH). Ce@UCNP-BCH can not only efficiently eliminate the SCI localized ROS, but dynamically monitor the oxidative state in the SCI repair process using a ratiometric luminescence signal. Moreover, the classic basso mouse scale score and immunofluorescence analysis together exhibit that Ce@UCNP-BCH effectively facilitates the regeneration of spinal cord including myelin sheath, and promotes the functional recovery of SCI mice. Particularly, the study combines snATAC-eq and snRNA-seq to reveal the heterogeneity of spinal cord tissue following Ce@UCNP-BCH treatment. The findings reveal a significant increase in myelinating oligodendrocytes, as well as higher expression of myelination-related genes, and the study also reveals the gene regulatory dynamics of remyelination after treatment. Besides, the ETLSA strategy synergistically boosts ROS consumption through the superoxide dismutase (SOD)-related pathways after SOD-siRNA treatment. In conclusion, this SETLSA strategy with simultaneously blocking and dynamic monitoring oxidative stress has enriched the toolkit for promoting SCI repair.

Keywords

cerium‐doped nanoenzymes; myelination; oxidative stress monitoring; reactive oxygen species (ROS); spinal cord injury (SCI).

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