{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:51:24Z","timestamp":1787961084766,"version":"build-2784847793"},"reference-count":190,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016350","name":"Sichuan Provincial Administration of Traditional Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016350","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>Chronic heart failure (CHF) poses a substantial global public health challenge, yet contemporary therapeutic strategies remain predominantly confined to hemodynamic compensation without reversing the fundamental myocardial bioenergetic failure. Mitochondrial dysfunction represents the core pathological driver of disease progression; however, conventional pharmacological agents encounter substantial barriers in traversing systemic biological obstacles and the mitochondrial double-membrane system to achieve precise organelle targeting. This review systematically delineates advances in the convergence of artificial intelligence (AI) and nanotechnology for mitochondria-targeted therapy in CHF. We first dissect the pathological mechanisms encompassing mitochondrial dynamics dysregulation, energetic collapse, and quality control failure. We subsequently elucidate how AI-engineered nanocarriers hierarchically navigate multiple physiological barriers from administration routes to mitochondrial membranes, with particular emphasis on machine learning-optimized antioxidant nanoformulations, biomimetic membrane encapsulation technologies, and synthetic mitochondria constructs. 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