A mitochondria-targeted fluoropolymer nanoparticle with inherent mitophagy-inducing and red fluorescence properties for treatment of atherosclerosis

Mengxiao Liang, Shengzhe Ruan, Qian Wang, Yuxue Cheng, Jiaqi Li, Changping Wang (), Yiyun Cheng () and Hui Wang ()
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Mengxiao Liang: South China University of Technology
Shengzhe Ruan: Shanghai Jiao Tong University School of Medicine
Qian Wang: Shanghai Jiao Tong University School of Medicine
Yuxue Cheng: South China University of Technology
Jiaqi Li: South China University of Technology
Changping Wang: Shanghai Jiao Tong University School of Medicine
Yiyun Cheng: East China Normal University
Hui Wang: South China University of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Mitophagy is crucial for the selective autophagic degradation of damaged mitochondria, helping to maintain both mitochondrial and cellular homeostasis. Here, we report a fluoroalkylated polypyridinium that specifically targets mitochondria and exhibits high activity in mitophagy induction. The polymer effectively restores mitochondrial function and alleviates the inflammatory response in foam cells by activating mitophagy, and displays inherent red fluorescence under physiological conditions, allowing for direct tracing of its biodistribution in cells and in vivo. Besides, the polymer nanoparticle shows high serum stability due to the antifouling properties of fluoroalkyl tags. After intravenous administration, the nanoparticle reduces oxidative stress, promotes mitophagy, and decreases cellular senescence in atherosclerotic plaques, contributing to high therapeutic efficacy. This study presents an innovative and effective strategy for the treatment of atherosclerosis and other mitochondrial dysfunction-related inflammatory conditions.

Date: 2025
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DOI: 10.1038/s41467-025-64813-0

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