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Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens. Its effective use as a cancer therapy requires a precisely targeted approach, which can be facilitated by using nanoparticles and nanomedicine, and their use to enhance ferroptosis is indeed a growing area of research. While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles, there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine. Furthermore, magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging (MRI). The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine. Here, recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized. This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine. Finally, image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations.

Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications. [ABSTRACT FROM AUTHOR]

Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens. Its effective use as a cancer therapy requires a precisely targeted approach, which can be facilitated by using nanoparticles and nanomedicine, and their use to enhance ferroptosis is indeed a growing area of research. While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles, there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine. Furthermore, magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging (MRI). The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine. Here, recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized. This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine. Finally, image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)