Nanomedicines Against Mitochondrial Dysfunction-Induced Metabolic Diseases

Mitochondrial dysfunction is a common pathology for metabolic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD). Nanomedicines provide a revolutionary strategy for mitochondrial function repair. They can realize targeted delivery, responsive release, and integration of multimodal therapies through nanotechnology and engineering and overcome limitations of traditional therapeutic methods, such as insufficient targeting, low bioavailability, and toxic side effects. In this article, the pathological characteristics of mitochondria are first introduced, and the relationship between mitochondrial dysfunction and metabolic diseases are illustrated. Structural features and design strategies of nanomedicines targeting mitochondrial dysfunction are summarized, with particular elaboration on targeting strategies and response mechanisms for diseased organs and subcellular organelles such as the liver, adipose tissue, atherosclerotic plaques, the brain, and mitochondria. The application and clinical translation of nanomedicines in obesity, atherosclerosis, diabetes, non-alcoholic fatty liver disease (NAFLD), and brain metabolic disorders are detailed. This article is concluded with a summary and outlook of the current research status, challenges, and future development directions.