Mitochondria-Targeted Nanoformulations: New Therapeutic Strategies and Opportunities for Cancer Immunotherapy

INTRODUCTION: Immunotherapy has revolutionized cancer treatment, however, its effectiveness remains limited by weak tumor immunogenicity and immunosuppressive microenvironments. Mitochondria have emerged as a strategic therapeutic target, given their central role in regulating immune cell activation, proliferation, and function through metabolic reprogramming and signaling pathway modulation. Mitochondria-targeted nanoformulations offer a promising approach to amplify anti-tumor immunity by enhancing immune responses at the cellular and molecular levels. METHODS: We searched the PubMed and Web of Science databases using keywords and combinations related to mitochondrial targeting, cancer, immunotherapy, and nanoformulations. The primary search timeframe focused on the last five years. The literature screening process mainly involved an initial screening based on titles and abstracts, followed by a full-text screening. RESULTS: Mitochondria critically govern anti-tumor immunity by controlling the activation and function of immune cells, modulating immune signaling pathways, and adjusting mitochondrial dynamics and metabolism. Recent advancements in mitochondria-targeted nanoformulations have shown potential to enhance immunity by inducing immunogenic cell death (ICD), regulating mitochondrial dynamics and metabolism, and activating key immune pathways. DISCUSSION: Mitochondrial-targeted is a novel strategy for activating anti-tumor immunity. Despite promising preclinical results, clinical translation remains unrealized. Future research must prioritize integrating basic and clinical studies to advance mitochondrial immunomodulation from bench to bedside. CONCLUSION: Although preclinical studies demonstrate the promise of mitochondria-targeted nanoformulations, clinical translation remains unrealized. Advances in nanotechnology, immunometabolism, and AI-driven drug design hold immense potential to overcome current barriers, particularly in solid tumors. Future efforts may establish mitochondrial immunomodulation as a transformative strategy in oncology.