Mitochondria-targeted nanoplatforms for tumor therapy: Design principles, applications, challenges and prospects

: As central regulators of cellular energy metabolism, redox homeostasis, and cell fate decisions, mitochondria undergo extensive functional reprogramming during tumorigenesis and disease progression. These alterations serve as critical molecular drivers of malignant evolution and significantly compromise the efficacy of conventional oncological interventions. Consequently, selective mitochondrial targeting in tumor cells has emerged as a compelling therapeutic strategy to restore treatment sensitivity and improve clinical outcomes. Nanotechnology-enabled, organelle-specific delivery platforms offer unprecedented spatiotemporal precision for mitochondrial intervention—ensuring high delivery efficiency, subcellular localization, and on-demand functionality—thereby establishing a transformative paradigm to overcome longstanding limitations in tumor therapy. This review comprehensively summarizes the fundamental design principles underpinning mitochondria-targeted nanoplatforms; critically assesses their innovative preclinical validation and emerging translational applications; and identifies key scientific, technical, and regulatory bottlenecks that impede clinical translation. We conclude by outlining concrete, actionable research directions to accelerate the rational development of next-generation precision oncology therapeutics grounded in mitochondrial targeting.