A Biomimetic PLK1 Nanodelivery System Promotes Migrasome‐Mediated Mitocytosis to Restore Efferocytosis and Functional Recovery After Spinal Cord Injury
5 affiliations
- 1Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China
- 2Cixi Biomedical Research Institute Wenzhou Medical University Ningbo Zhejiang China
- 3Department of Spine Surgery Peking University Fourth School of Clinical Medicine Beijing China
- 4Department of Neurology The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
- 5Department of Spine Surgery Beijing Jishuitan Hospital Capital Medical University Beijing China
Abstract
Excessive accumulation and insufficient clearance of apoptotic cells following spinal cord injury (SCI) are key factors contributing to persistent injury. Macrophage efferocytosis is essential for resolving injury but is compromised by mitochondrial dysfunction and lysosomal overload. Maintaining mitochondrial functional homeostasis is therefore crucial for preserving the acidic lysosomal environment, alleviating the cellular lysosomal burden, and sustaining efferocytosis. Common mitochondrial quality control (MQC) pathways such as mitophagy increase the lysosomal burden. Here, we investigated how polo‐like kinase 1 (PLK1) regulates macrophage efferocytosis and elucidated the underlying mechanism of migrasome‐mediated mitocytosis. We demonstrate that PLK1 regulates TSPAN4‐dependent migrasome formation, which drives the selective extrusion of damaged mitochondria, alleviates the lysosomal burden, and increases efferocytic capacity. To enable targeted PLK1 delivery, we engineered macrophage membrane‐coated, reactive oxygen species (ROS)‐responsive nanocomplexes encapsulating PLK1 plasmids (MM‐NPs@PLK1). This biomimetic nanoplatform preferentially accumulates in the injured spinal cord, promotes macrophage‐associated PLK1 delivery, enhances mitocytosis and efferocytosis, supports neural tissue repair, and significantly improves locomotor recovery in SCI mice. In summary, our study reveals a PLK1‐regulated MQC mechanism that sustains macrophage efferocytosis through migrasome‐mediated mitocytosis, providing a promising therapeutic strategy for SCI.
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BibTeX
@article{hu2026biomimetic,
title = {{A Biomimetic PLK1 Nanodelivery System Promotes Migrasome‐Mediated Mitocytosis to Restore Efferocytosis and Functional Recovery After Spinal Cord Injury}},
author = {Zhenxin Hu and Haoli Wang and Jing Huang and Junhua Zhou and Jialong Hou and Hanwei Miao and Huixin Tan and Yining Wang and Hao Hu and Na Li and Pengcheng Qiu and Hongyu Zhang and Da He and Qingqing Wang},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.78367},
url = {https://doi.org/10.1002/advs.78367},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Biomimetic PLK1 Nanodelivery System Promotes Migrasome‐Mediated Mitocytosis to Restore Efferocytosis and Functional Recovery After Spinal Cord Injury
AU - Zhenxin Hu
AU - Haoli Wang
AU - Jing Huang
AU - Junhua Zhou
AU - Jialong Hou
AU - Hanwei Miao
AU - Huixin Tan
AU - Yining Wang
AU - Hao Hu
AU - Na Li
AU - Pengcheng Qiu
AU - Hongyu Zhang
AU - Da He
AU - Qingqing Wang
PY - 2026
DA - 2026/10/26
JO - Advanced Science
DO - 10.1002/advs.78367
UR - https://doi.org/10.1002/advs.78367
AB - Excessive accumulation and insufficient clearance of apoptotic cells following spinal cord injury (SCI) are key factors contributing to persistent injury. Macrophage efferocytosis is essential for resolving injury but is compromised by mitochondrial dysfunction and lysosomal overload. Maintaining mitochondrial functional homeostasis is therefore crucial for preserving the acidic lysosomal environment, alleviating the cellular lysosomal burden, and sustaining efferocytosis. Common mitochondrial quality control (MQC) pathways such as mitophagy increase the lysosomal burden. Here, we investigated how polo‐like kinase 1 (PLK1) regulates macrophage efferocytosis and elucidated the underlying mechanism of migrasome‐mediated mitocytosis. We demonstrate that PLK1 regulates TSPAN4‐dependent migrasome formation, which drives the selective extrusion of damaged mitochondria, alleviates the lysosomal burden, and increases efferocytic capacity. To enable targeted PLK1 delivery, we engineered macrophage membrane‐coated, reactive oxygen species (ROS)‐responsive nanocomplexes encapsulating PLK1 plasmids (MM‐NPs@PLK1). This biomimetic nanoplatform preferentially accumulates in the injured spinal cord, promotes macrophage‐associated PLK1 delivery, enhances mitocytosis and efferocytosis, supports neural tissue repair, and significantly improves locomotor recovery in SCI mice. In summary, our study reveals a PLK1‐regulated MQC mechanism that sustains macrophage efferocytosis through migrasome‐mediated mitocytosis, providing a promising therapeutic strategy for SCI.
SN - 2198-3844
ER -