Nanotechnology-mediated metabolic reprogramming for tumour ferroptosis: mechanisms and therapeutic prospects

Abstract

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy for tumours resistant to conventional treatments. However, tumour cells frequently develop ferroptosis resistance through adaptive metabolic reprogramming mechanisms, such as enhancing antioxidant defences and altering nutrient utilization, both of which help maintain redox homeostasis and reduce oxidative damage. By leveraging the advantageous properties of nanomaterials, including tumour-targeting ability, controlled drug release, and multimodal synergistic capabilities, nanotechnology-mediated metabolic intervention has recently gained significant attention as a means to induce tumour ferroptosis. This review focuses on nano-based strategies that selectively disrupt key metabolic processes, such as iron homeostasis, lipid metabolism, amino acid metabolism, and glucose metabolism, thereby restoring susceptibility to ferroptosis. Finally, we discuss the current challenges and future prospects of nanotechnology-driven ferroptosis therapy, with the goal of providing theoretical insight and innovative directions for developing effective antitumour strategies.