Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy

Ferroptosis is a non-apoptotic programmed cell death caused by the accumulation of lipid peroxide. System Xc-/glutathione peroxidase 4 (GPX4) axis and iron axis are two main pathways regulating ferroptosis. Simultaneously, multiple pathways are also involved in the ferroptosis regulation. Ferroptosis is an intense area of the current study. With the improvement of the regulatory mechanisms that underlie ferroptosis, a variety of drugs associated with ferroptosis have been discovered and developed for cancer therapy. Among them, traditional drugs were developed initially. Small molecule compounds that regulate ferroptosis signaling pathway and iron complexes that promote the Fenton reaction have become important drugs for inducing ferroptosis. In recent years, the emerging development of nanotechnology has promoted the research of ferroptosis nanodrugs. Iron-based nanomaterials are extensively tested as ferroptosis-inducing agents. Furthermore, nanoscale drug delivery systems offer a suitable scaffold for traditional drug therapies. Traditional drugs and nanodrugs are complementary, each with their own strengths and limitations. This review describes the latest studies on the regulation of ferroptosis in tumor cells and focuses on the entanglement between traditional drugs and nanodrugs. To conclude, the challenges and perspectives in this field are put forward.