OSCR

Dual-targeting nanoparticles enhance microglial P2Y12R expression to promote neuronal mitophagy for repairing spinal cord injury.

Overview

Authors: Zhenming Tian1,2,3, Hong Li1,2,3, Yunheng Jiang1,2,3, Huiye Wei4, Yubao Lu1,2,3, Senyu Yao1,2,3, Mao Pang1,2,3, Xintao Shuai4, Bin Liu1,2,3, Limin Rong1,2,3
ORCID iDs: Yubao Lu, Xintao Shuai, Limin Rong
  1. Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
  2. Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, Guangzhou, China
  3. Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, China
  4. Nanomedicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Institutions: Third Affiliated Hospital of Sun Yat-sen University (China)
Journal: Cell death & disease, volume 17, issue 1, article 516
Dates: received 3 June 2025; accepted 9 March 2026; published online 19 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41419-026-08596-2 · PMID 42002569 · PMCID PMC13221473 · OpenAlex W7154888543
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: Biomedical materials, Neuroimmunology, Cell death in the nervous system, Genetic vectors, Spinal cord injury
MeSH: Gene Transfer Techniques*, Genetic Therapy*, Microglia*, Mitophagy*, Nanoparticles*, Nerve Regeneration*, Receptors, Purinergic P2Y12*, Spinal Cord Injuries*, Animals, Female, Mice, Mice, Inbred C57BL, Mitochondria, Neurons, Plasmids, Reactive Oxygen Species (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (82072455, 82102642, 82172433, U22A20297, 823B2060, 82372400); China Postdoctoral Science Foundation (GZB20240904)
Citations: cited by 1 paper (Europe PMC); 41 references in the paper

Abstract

Spinal cord injury (SCI) leads to severe mitochondrial dysfunction and ROS cascade, with microglia playing a dual role in both exacerbating damage and providing neuroprotection. Recent evidence has highlighted the importance of P2Y12R in microglial-neuron interactions, particularly in modulating mitochondrial quality control and mitigating oxidative stress. Here, we develop a dual-targeting nanoparticle system (P2Y-TK-Nano) to enhance P2Y12R expression in microglia and promote neuronal mitophagy, aiming to reduce mitochondrial reactive oxygen species (mtROS) and improve neuronal survival following SCI. The P2Y-TK-Nano system combines a ROS-responsive thioketal bond for injury-site targeting with an MG1 peptide to selectively target microglia. This design enables precise nanoparticle delivery to the ROS-enriched injury microenvironment, effectively restoring P2Y12R expression in microglia. Microglia treated with P2Y-TK-Nano exhibit elevated P2Y12R expression, leading to increased interaction with injured neurons, improved mitophagy, and reduced mtROS production. These combined effects significantly attenuate secondary damage and contribute to neuroprotection post-SCI. Our findings reveal a novel regulatory mechanism by which P2Y12R overexpression in microglia enhances neuronal mitophagy and mitigates oxidative stress after SCI. The dual-targeting P2Y-TK-Nano system offers a promising therapeutic approach to address microglial activation and mitochondrial dysfunction in the context of SCI.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 16 MeSH terms, 2 funders, 41 references.

Cite

This paper

Tian, Z., Li, H., Jiang, Y., Wei, H., Lu, Y., Yao, S., Pang, M., Shuai, X., Liu, B., & Rong, L. (2026). Dual-targeting nanoparticles enhance microglial P2Y12R expression to promote neuronal mitophagy for repairing spinal cord injury. Cell death & disease, 17(1), 516. https://doi.org/10.1038/s41419-026-08596-2

BibTeX

@article{tian2026dual,
author = {Tian, Zhenming and Li, Hong and Jiang, Yunheng and Wei, Huiye and Lu, Yubao and Yao, Senyu and Pang, Mao and Shuai, Xintao and Liu, Bin and Rong, Limin},
title = {{Dual-targeting nanoparticles enhance microglial P2Y12R expression to promote neuronal mitophagy for repairing spinal cord injury}},
journal = {Cell death \& disease},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {516},
publisher = {Nature Publishing Group},
issn = {2041-4889},
doi = {10.1038/s41419-026-08596-2},
url = {https://doi.org/10.1038/s41419-026-08596-2},
pmid = {42002569},
pmcid = {PMC13221473}
}

RIS

TY - JOUR
AU - Tian, Zhenming
AU - Li, Hong
AU - Jiang, Yunheng
AU - Wei, Huiye
AU - Lu, Yubao
AU - Yao, Senyu
AU - Pang, Mao
AU - Shuai, Xintao
AU - Liu, Bin
AU - Rong, Limin
TI - Dual-targeting nanoparticles enhance microglial P2Y12R expression to promote neuronal mitophagy for repairing spinal cord injury
T2 - Cell death & disease
J2 - Cell Death Dis
PY - 2026
DA - 2026/04/19
VL - 17
IS - 1
SP - 516
SN - 2041-4889
PB - Nature Publishing Group
DO - 10.1038/s41419-026-08596-2
UR - https://doi.org/10.1038/s41419-026-08596-2
LA - en
ER -

CSL-JSON

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