Mechanistic pathways and therapeutic opportunities of nanoparticle-mediated ferroptosis in cancer

Cancer remains one of the most lethal diseases worldwide, posing a significant challenge to modern medicine. Conventional cancer treatments mostly depend on triggering apoptosis; nevertheless, their effectiveness is sometimes undermined by the inherent or developed resistance to apoptosis in tumor cells. Ferroptosis, an iron-dependent mechanism of controlled cell death characterized by lipid peroxidation, has emerged as a prospective therapeutic target for tumors, as it entirely circumvents traditional apoptotic pathways to eliminate multidrug-resistant and highly aggressive cancer cells. However, its clinical application is hindered by limitations in bioavailability, delivery efficiency, and solubility. Recent advances in nanotechnology have enabled the development of nanoparticle-based drug delivery systems, which enhance targeted therapy while minimizing off-target effects. Nanoparticle-mediated ferroptosis represents a promising strategy for cancer treatment. This review summarizes the molecular mechanisms of ferroptosis and evaluates recent advances in nanoparticle-mediated ferroptosis in antitumor therapy, ultimately synthesizing the synergistic advantages of these engineered nanomaterials and outlining the critical translational challenges that must be overcome to facilitate their future clinical implementation.