Mitochondria-targeted drug delivery in cancers

Mitochondria are considered one of the most important subcellular organelles for targeting and delivering drugs because mitochondria are the main location for various cellular functions and energy (i.e., ATP) production, and mitochondrial dysfunctions and malfunctions cause diverse diseases such as neurodegenerative disorders, cardiovascular disorders, metabolic disorders, and cancers. In particular, unique mitochondrial characteristics (e.g., negatively polarized membrane potential, alkaline pH, high reactive oxygen species level, high glutathione level, high temperature, and paradoxical mitochondrial dynamics) in pathological cancers have been used as targets, signals, triggers, or driving forces for specific sensing/diagnosing/imaging of characteristic changes in mitochondria, targeted drug delivery on mitochondria, targeted drug delivery/accumulation into mitochondria, or stimuli-triggered drug release in mitochondria. In this review, we describe the distinctive structures, functions, and physiological properties of cancer mitochondria and discuss recent technologies of mitochondria-specific "key characteristic" sensing systems, mitochondria-targeted "drug delivery" systems, and mitochondrial stimuli-specific "drug release" systems as well as their strengths and weaknesses.