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

Abstract

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.

Black Phosphorus Quantum Dots Effectively and Safely Treat Glaucoma as a Promising Anti-Ferroptosis Nano-drug

“…Firstly, BPQDs, as a highly safe nanomedicine, overcome the limitations of traditional small molecule drugs, such as uncertain safety, short half-life, low bioavailability, poor targeting, and unstable e cacy 16,17 . Secondly, BPQDs possess a relatively loose molecular structure and abundant surface active sites 66,67 , allowing them to adsorb and undergo covalent bonding with other drugs.…”

“…Moreover, the safety of other available ferroptosis inhibitors within the eye still needs to be determined. These ferroptosis inhibitors are all small-molecule drugs with potential drawbacks such as a short half-life, low bioavailability, poor targeting, and unstable e cacy 16,17 . Thus, a more suitable and safer ferroptosis inhibitor (especially a nano-drug) is urgently required, which will signi cantly facilitate the treatment of glaucoma and other ferroptosis-related diseases.…”

The application of nanoparticles based on ferroptosis in cancer therapy

“…In recent years, the development of ferroptosis nanoparticles has been promoted by research on nano-delivery systems. 116 Most ferroptosis inducers are small molecule drugs that have direct effects on disease targets. Small molecule drugs also have the cost advantages of low price and mature technology.…”

Recent progress in biomaterials-driven ferroptosis for cancer therapy

“…Ferroptosis was discovered long before the concept of ferroptosis was established in 2012. 1 Several studies have revealed that controlling or triggering ferroptosis can be advantageous in the treatment of various medical conditions, such as degenerative diseases, ischemic organ damage and cancer. 2,3 For cancer treatment, traditional treatments, including surgery, chemotherapy, and radiation therapy, are often not as effective as desired due to factors like drug resistance, treatment efficiency, and toxic side effects.…”