Ferroptosis nanomedicine for cancer therapy: strategies and challenges

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, and it has become an attractive strategy for cancer therapy because it can target redox and metabolic vulnerabilities that differ from those exploited by apoptosis-based treatments. Small-molecule ferroptosis inducers have clarified the therapeutic logic of this pathway, but their use in cancer treatment requires control over pharmacokinetics, tumor selectivity, local activation and systemic safety. Nanomedicine offers a programmable route to address these requirements. Engineered nanoplatforms can supply catalytic iron, remodel the tumor redox state, deplete antioxidant defenses, carry ferroptosis inducers, respond to tumor microenvironmental cues and combine ferroptosis with phototherapy, sonodynamic therapy, chemotherapy, radiotherapy or immunotherapy. Yet the field remains largely preclinical, and translation will depend on biodistribution, degradability, metal-related toxicity, manufacturing reproducibility, pharmacodynamic biomarkers and rational patient selection. This review summarizes the biological rationale for ferroptosis-targeted cancer therapy, analyzes major translational barriers, and synthesizes nanomedicine strategies that may move ferroptosis induction from experimental proof of concept toward clinically interpretable intervention.