2. Academic Validation
  3. Extracellular Vesicle-Mediated Precision Delivery of Paclitaxel Activates Mitophagy to Promote Repair after Spinal Cord Injury

Extracellular Vesicle-Mediated Precision Delivery of Paclitaxel Activates Mitophagy to Promote Repair after Spinal Cord Injury

  • ACS Nano. 2026 Mar 24;20(11):9387-9406. doi: 10.1021/acsnano.5c21273.
Shuxian Zhao 1,  Liqun Duan 2,  Zuogang Lv 3,  Zhiqiang Han 2,  Wenbin Xu 2,  Kaikai Zhang 2,  Wei Liu 4,  Jiaxiang Bai 2,  Weihua Cai 5,  Wenzhi Zhang 2,  Yufeng Gao 1,  Yuluo Rong 2 6
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Anhui Province Key Laboratory of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui, China.
  • 2 Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China.
  • 3 Department of Orthopedics, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 238001, Anhui, China.
  • 4 Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
  • 6 State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400038, China.
PMID: 41773788 DOI: 10.1021/acsnano.5c21273
Abstract

Spinal cord injury (SCI) is a debilitating disorder characterized by intricate pathological processes that result in severe motor and sensory deficits. Existing therapeutic approaches remain insufficient to achieve comprehensive functional restoration, indicating the necessity of alternative treatment strategies. In this study, an advanced nanoparticle-based drug delivery system was established using extracellular vesicles (EVs) modified with a matrix metalloproteinase (MMP)-responsive peptide, ACPP, to achieve the targeted delivery of paclitaxel (PTX). The ACPP-EVs@PTX formulation integrates the drug loading capacity of EVs, the lesion-targeting capability conferred by ACPP, and the neuroprotective properties of PTX. Enhanced accumulation of PTX at the SCI lesion site was achieved, accompanied by a reduction in the off-target distribution. Both in vitro and in vivo experiments demonstrated marked therapeutic efficacy of ACPP-EVs@PTX through modulation of the SCI microenvironment, including stimulation of angiogenesis, attenuation of inflammatory responses, alleviation of oxidative stress, and promotion of axonal regeneration. In addition, the activation of PINK1-Parkin-mediated Mitophagy was observed, leading to improved mitochondrial function and enhanced neuronal repair. Behavioral evaluations further confirmed significant recovery of neurological function, supporting the translational potential of this multitarget, synergistic therapeutic strategy. Collectively, this work establishes an integrated therapeutic strategy for spinal cord repair and supports its translational potential.

Keywords

ACPP-modified system; extracellular vesicles; mitophagy; multitarget drug delivery; paclitaxel; spinal cord injury.

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