Ferroptosis: challenges and opportunities for nanomaterials in cancer therapy

Abstract

Ferroptosis, a completely new form of regulated cell death, is mainly caused by an imbalance between oxidative damage and reductive protection and has shown great anti-cancer potential. However, existing small-molecule ferroptosis inducers have various limitations, such as poor water solubility, drug resistance, and low targeting ability, hindering their clinical applications. Nanotechnology provides new opportunities for ferroptosis-driven tumor therapy. Especially, stimuli-responsive nanomaterials stand out among others and have been widely researched because of their unique spatiotemporal control advantages. Therefore, it’s necessary to summarize the application of those stimuli-responsive nanomaterials in ferroptosis. Here, we describe the physiological feature of ferroptosis and illustrate current challenges to induce ferroptosis for cancer therapy. Then, nanomaterials that induce ferroptosis are classified and elaborated according to external and internal stimuli. Finally, the future perspectives in the field are proposed. We hope this review facilitate paving the way for the design of intelligent nano ferroptosis inducers.

Designing Smart Iron Oxide Nanoparticles for MR Imaging of Tumors

“…The metal participates in various biological processes, both physiological and pathophysiological . However, excess iron deposition in the body will cause iron overload, which can lead to deleterious effects to organs or other complications. , In addition, large IONPs are metabolized to labile iron rather than excreted, catalyzing hydroxyl radical production from ferrous iron, which can damage DNA, lipids, and proteins within cells . Thus, sophisticated methods are urgently needed to reveal shifts in the valency of iron under various conditions and monitor the effect on the subsequent biological processes.…”

The application of nanoparticles based on ferroptosis in cancer therapy

“…Some of these stimuli not only control drug release and improve drug enrichment but also enhance the efficacy of ferroptosis treatment through synergistic treatment. 204,205 Finally, the in situ self-assembly strategy of ferroptosis nanoparticles is based on molecular state cycling, self-assemblyassisted targeting to the tumor site, and the aggregation/ assembly-induced retention (AIR) effect, which reduces the problems of rapid excretion and extensive metabolism. This strategy reduces systemic toxicity and improves biocompatibility.…”

Recent progress in biomaterials-driven ferroptosis for cancer therapy

“…Together, these factors make the combination of ferroptosis and biomedical nanomaterials a promising treatment for cancer therapy. 16,17 Recently, due to the good physical and chemical properties of nanomaterials, many nanotechnology experts have focused on cancer treatment. More and more biomedical nanomaterials have been widely studied as nanomaterialbased anticancer drug delivery systems.…”