Stimuli-responsive ferroptosis for cancer therapy

Abstract

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective in treating conventional drug-resistant tumors.

Intracellular self-aggregation of biomimetic Fe3O4 nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

“…5–7 The unique induction mechanism has prompted ferroptosis therapy to bring new opportunities for the treatment of cancer and other diseases. 8–10…”

Endoplasmic Reticulum-Targeting Quinazolinone-Based Lipophilic Probe for Specific Photoinduced Ferroptosis and Its Induced Lipid Dynamic Regulation

“…15,16 Therefore, the development of new types of small organic molecules as ferroptosis inducers not only provides chemical tools for exploring the mechanism of ferroptosis initiation and execution but also provides new options for the treatment of tumors, especially drug-resistant tumors. 9,17,18 Although an excess of lipid peroxidation is the primary trigger for ferroptosis initiation and execution, 19 increased lipid peroxidation in cells has also been linked to other types of programmed cell death, such as pyroptosis or oxidative stressinduced cell death. 20,21 Currently, the small organic molecules used for specific ferroptosis induction exert their function mainly by inhibiting important antioxidant proteins involved in ferroptosis defense systems, which destroy the redox balance and cause the accumulation of lethal lipid peroxidation in cells.…”

Multifunctional Tumor-Targeting Carbon Dots for Tumor Microenvironment Activated Ferroptosis and Immunotherapy in Cancer Treatment

“…The unique tumor microenvironment (TME) can support the rapid growth of tumor cells, which is characterized by the presence of high expression of glutathione (GSH) and a weakly acidic and hypoxic environment. − Compared with normal tissues, the abundant GSH existing in the TME, with its inherent reducibility, is of utmost importance in the regulation of tumor-related redox homeostasis. , In particular, ferroptosis levels would be attenuated by highly expressed GSH, which is characterized by excessive production and accumulation of hydroxyl radicals (·OH) and lipid peroxidation (LPO). , Thus, depleting intracellular GSH is considered an important strategy to enhance ferroptosis. − However, depletion of GSH alone is not sufficient to increase the effect of intracellular oxidative stress, and the increase in reactive oxygen species (ROS) is also an efficient strategy to trigger the accumulation of LPO, leading to an enhanced ferroptosis therapy . At present, to increase intracellular ROS, transition-metal-containing nanoparticles (such as Fe-containing nanoparticles) have been rapidly developed to convert the intracellular H 2 O 2 into ·OH through Fenton/Fenton-like reaction. ,, However, the Fe 2+ -involved Fenton reaction is greatly limited by the weakly acidic TME. , Comparatively, Cu + -catalyzed Fenton-like reaction could be suitable for the weakly acidic TME, and the efficiency of catalysis is up to 160 times that of Fe 2+ . , Therefore, it is necessary to develop copper-based nanoparticles with high catalytic activity for tumor therapy …”