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Existing antioxidants can only scavenge ROS and cannot address the root cause of ROS production, namely, abnormal mitochondria. To overcome this limitation, the study develops a piezoelectric synergistic drug\u2010loaded nanosystem (BaTCG nanosystem) that targets mitochondria. The BaTCG nanosystem is delivered to mitochondria via triphenylphosphine modification, and generates current under the stimulation of ultrasound, thereby promoting mitochondrial autophagy and restoring mitochondrial\u00a0 homeostasis. In a model of diabetes\u2010related erectile dysfunction (ED), the BaTCG nanosystem, through the current induced by the piezoelectric effect, not only promoted mitophagy, thereby reducing ROS production, but also released long\u2010acting glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) to effectively reduce blood glucose levels and mitochondrial damage. Each component of this nanosystem functions individually as well as synergistically, thus facilitating corpus cavernosum repair and restoring erectile function. In conclusion, the findings offer a novel therapeutic strategy for diabetes\u2010related ED and a target for the treatment of diabetes\u2010related conditions with functionalized nanoparticles to regulate mitophagy.<\/jats:p>","DOI":"10.1002\/adma.202413287","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T03:36:47Z","timestamp":1734406607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A Mitochondrion\u2010Targeting Piezoelectric Nanosystem for the Treatment of Erectile Dysfunction via Autophagy Regulation"],"prefix":"10.1002","volume":"37","author":[{"given":"Shuting","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of Technology  Guangzhou 510006 China"},{"name":"School of Materials Science and Engineering South China University of Technology  Guangzhou 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