Emerging Strategies of Cancer Therapy Based on Ferroptosis

Abstract

Ferroptosis, a new form of regulated cell death that is iron- and reactive oxygen species dependent, has attracted much attention in the research communities of biochemistry, oncology, and especially material sciences. Since the first demonstration in 2012, a series of strategies have been developed to induce ferroptosis of cancer cells, including the use of nanomaterials, clinical drugs, experimental compounds, and genes. A plethora of research work has outlined the blueprint of ferroptosis as a new option for cancer therapy. However, the published ferroptosis-related reviews have mainly focused on the mechanisms and pathways of ferroptosis, which motivated this contribution to bridge the gap between biological significance and material design. Therefore, it is timely to summarize the previous efforts on the emerging strategies for inducing ferroptosis and shed light on future directions for using such a tool to fight against cancer. Here, the current strategies of cancer therapy based on ferroptosis will be elaborated, the design considerations and the advantages and limitations are highlighted, and finally a future perspective on this emerging field is given.

Recent Progress in Ferroptosis Inducers for Cancer Therapy

“…These discoveries pave the way for nanoparticle‐triggered ferroptosis. In recent years, ferroptosis mechanism has been taken into consideration for nanomedicine‐mediated cancer therapy, exemplified by the rapid development of nano ferroptosis inducers …”

“…In recent years, ferroptosis mechanism has been taken into consideration for nanomedicine-mediated cancer therapy, exemplified by the rapid development of nano ferroptosis inducers. [112,113] For designing of nano ferroptosis inducers, an intuitional method is to incorporate small molecule ferroptosis inducers into nano delivery vehicles. Compared with free drugs, nanoplatforms enable improved solubility and biocompatibility, as well as increased tumor accumulation by either active or passive targeting.…”

MicroRNA‐214‐3p enhances erastin‐induced ferroptosis by targeting ATF4 in hepatoma cells

“…These ferroptosis inducers exert antitumor activities in many types of malignancies (Dachert, Schoeneberger, Rohde, & Fulda, 2016; Sato et al, 2018; Shintoku et al, 2017), including HCC (Nie, Lin, Zhou, Wu, & Zheng, 2018; Sun et al, 2016). Although inducing ferroptosis is a promising anticancer strategy, the negative regulators of ferroptosis which inhibit cellular iron uptake and/or limit ROS production may hinder the application of ferroptosis inducers in anticancer therapy (Shen et al, 2018; Xie et al, 2016). Activating transcription factor 4 (ATF4) is an essential mediator of endoplasmic reticulum (ER) stress (Bi et al, 2005).…”

“…Although inducing ferroptosis is a promising anticancer strategy, the negative regulators of ferroptosis which inhibit cellular iron uptake and/or limit ROS production may hinder the application of ferroptosis inducers in anticancer therapy (Shen et al, 2018;Xie et al, 2016). Activating transcription factor 4 (ATF4) is an essential mediator of endoplasmic reticulum (ER) stress (Bi et al, 2005).…”

Tumor Microenvironment‐Triggered Aggregated Magnetic Nanoparticles for Reinforced Image‐Guided Immunogenic Chemotherapy

“…[8] Since discovered in 2012, ferroptosis has been widely known as an iron-and ROS-dependent form of cell death. [9] Catalyzed by Fe 3+ or Fe 2+ (so-called Fenton's reaction), the intracellular hydrogen peroxide (H 2 O 2 ) would be rapidly converted to highly reactive hydroxyl radical (·OH), causing a high ROS stress and resulting in irreversible oxidative damage to lipids, proteins and DNA, eventually cell ferroptosis. [10] More importantly, several studies have found that ferroptotic agents could induce an unfolded protein response and subsequently activated a series of ER stress-mediated ferroptotic signaling pathways, [11] which fits in with our demand for enhanced treatment strategy.…”