Advances in mitochondria-targeted nanoparticles for lung cancer therapy

Lung cancer is one of the most commonly diagnosed and lethal malignancies worldwide. Although multimodal treatment has advanced substantially, therapeutic resistance, recurrence, and metastasis remain major clinical challenges. Mitochondria regulate cellular bioenergetics, redox homeostasis, and cell death and therefore contribute substantially to lung cancer development and progression. These functions make mitochondrial targeting a promising therapeutic strategy. However, mitochondrial delivery requires traversal of multiple biological barriers, and free drug molecules rarely accumulate efficiently within mitochondria. Nanoparticles offer tunable structures, high drug-loading capacity, and readily modifiable surfaces. By combining lung cancer cell targeting with mitochondrial targeting ligands, they can deliver drugs precisely to mitochondria in lung cancer cells. This review outlines mitochondrial vulnerabilities in lung cancer and summarizes mechanisms, design strategies, and recent advances in mitochondria-targeted nanoparticles. We also discuss their potential value and challenges for clinical translation.