A dual-action nanoparticle approach for spinal cord injury treatment: ferroptosis inhibition, inflammation control, and Myelin preservation

J Nanobiotechnology. 2026 Feb 12;24(1):158. doi: 10.1186/s12951-026-04114-w.

Chang Xue ¹ ² ³, Yicheng Zhou ¹, Huixin Lin ¹, Zijun Li ¹, Yuxin Xiao ¹ ³, Jinfeng Yang ¹ ³, Mengqi Lu ¹ ³, Yuwen Qin ¹ ³, Dawei Song ³, Wei Chen ³, Junpeng Xu ⁴, Yanming Zuo ⁵, Zhouguang Wang ⁶ ⁷, Chengxi Jiang ⁸ ⁹ ¹⁰

Affiliations

1 National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
2 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea.
3 Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou, 247100, China.
4 National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. [email protected].
5 National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. [email protected].
6 National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. [email protected].
7 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China. [email protected].
8 National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. [email protected].
9 Jiuhuashan Polygonati Rhizoma Research Institute, Chizhou, 247100, China. [email protected].
10 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China. [email protected].

PMID: 41673859 DOI: 10.1186/s12951-026-04114-w

Abstract

Spinal cord injury (SCI) initiates secondary injury cascades, including Ferroptosis and neuroinflammation, which contribute to progressive neuronal and myelin loss. Single-cell RNA Sequencing defines a therapeutically actionable window for selenium (Se) replenishment: neuronal and oligodendrocyte selenoproteins-especially Gpx4-show a transient rise at 1-day post-injury followed by sustained suppression with induction of Ferroptosis drivers, indicating Se-limited antioxidant collapse. In this study, we extracted a novel Polygonatum-derived fructan and, for the first time, used it to coat selenium nanoparticles, synthesizing PRP@SeNPs via a green, ascorbate-mediated reduction. The PRP coating yields smaller hydrodynamic size, a more negative zeta potential, and a front-loaded yet sustained Se-release profile that aligns with the scRNA-seq-identified supplementation window. In vitro, PRP@SeNPs restore Gpx4 expression, reduce lipid peroxidation, scavenge ROS, and promote M2 microglial polarization. In situ administration in a T-cut SCI mouse model suppresses Ferroptosis and glial activation, preserves neuronal and myelin integrity, enhances axonal regeneration, and improves motor function (Basso Mouse Scale, gait analysis, electrophysiology). PRP@SeNPs thus provide a drug-free, biocompatible nanotherapeutic strategy to replenish Se, mitigate secondary injury mechanisms, and promote neuroprotection and remyelination for advanced functional recovery after SCI.

Keywords

Polygonatum polysaccharide; Ferroptosis; Neuroinflammation; Selenium nanoparticles; Spinal cord injury.

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HY-129457

FINO2

98.0%, Ferroptosis Inducer

Ferroptosis

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