Mitochondrial dysfunction-targeted nanosystems for precise tumor therapeutics

Mitochondria play critical roles in the regulation of the proliferation and apoptosis of cancerous cells. Targeted induction of mitochondrial dysfunction in cancer cells by multifunctional nanosystems for cancer treatment has attracted increasing attention in the past few years. Numerous therapeutic nanosystems have been designed for precise tumor therapy by inducing mitochondrial dysfunction, including reducing adenosine triphosphate, breaking redox homeostasis, inhibiting glycolysis, regulating proteins, membrane potential depolarization, mtDNA damage, mitophagy dysregulation and so on. Understanding the mechanisms of mitochondrial dysfunction would be helpful for efficient treatment of diseases and accelerating the translation of these therapeutic strategies into the clinic. Then, various strategies to construct mitochondria-targeted nanosystems and induce mitochondrial dysfunction are summarized, and the recent research progress regarding precise tumor therapeutics is highlighted. Finally, the major challenges and an outlook in this rapidly developing field are discussed. This review is expected to inspire further development of novel mitochondrial dysfunction-based strategies for precise treatments of cancer and other human diseases.