Nanotechnology-integrated ferroptosis inducers: a sharp sword against tumor drug resistance

Presently, the biggest hurdle to cancer therapy is the inevitable emergence of drug resistance. Since conventional therapeutic schedules fall short of the expectations in curbing drug resistance, the development of novel drug resistance management strategies is critical. Extensive research over the last decade has revealed that the process of ferroptosis is correlated with cancer resistance; moreover, it has been demonstrated that ferroptosis inducers reverse drug resistance. To elucidate the development and promote the clinical transformation of ferroptosis strategies in cancer therapy, we first analyzed the roles of key ferroptosis-regulating molecules in the progression of drug resistance in-depth and then reviewed the design of ferroptosis-inducing strategies based on nanotechnology for overcoming drug resistance, including glutathione depletion, reactive oxygen species generation, iron donation, lipid peroxidation aggregation, and multiple-drug resistance-associated tumor cell destruction. Finally, the prospects and challenges of regulating ferroptosis as a therapeutic strategy for reversing cancer therapy resistance were evaluated. This review aimed to provide a comprehensive understanding for researchers to develop ferroptosis-inducing nanoplatforms that can overcome drug resistance.