Finding molecules or nanoparticles that selectively target mitochondria and induce improved function is the most developed of the various strategies that might be employed to at least partially reverse the age-related loss of mitochondrial capacity thought to be important in age-related disease and dysfunction. Most of the small molecules developed to date appear to work by improving mitophagy, the processes of quality control that recycle worn and dysfunctional mitochondria, but the precise details of the mechanisms involved are incompletely understood. Mitophagy itself is incompletely understood. Continuing this trend, researchers here present a nanoparticle that is observed to improve mitochondrial function and thus cell function via improved mitophagy.
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.
Link: https://doi.org/10.1038/s41467-025-64813-0
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