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      Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging

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          Abstract

          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.

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          Highlights

          • Recent advances in the use of magnetic nanoparticles for ferroptosis cancer nanomedicine are summarized.

          • The advantages of image-guided ferroptosis cancer nanomedicine are overviewed.

          • The rational design and fabrication of magnetic nanoparticles to enhance local ferroptosis induction are described.

          • Challenges and opportunities for image-guided ferroptosis cancer nanomedicine in clinical applications are provided.

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          Most cited references224

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          Cancer statistics, 2023

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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            Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

            Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
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              Regulation of ferroptotic cancer cell death by GPX4.

              Ferroptosis is a form of nonapoptotic cell death for which key regulators remain unknown. We sought a common mediator for the lethality of 12 ferroptosis-inducing small molecules. We used targeted metabolomic profiling to discover that depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in response to one class of compounds and a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compounds. GPX4 overexpression and knockdown modulated the lethality of 12 ferroptosis inducers, but not of 11 compounds with other lethal mechanisms. In addition, two representative ferroptosis inducers prevented tumor growth in xenograft mouse tumor models. Sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPX4-regulated ferroptosis. Thus, GPX4 is an essential regulator of ferroptotic cancer cell death. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                29 September 2023
                February 2024
                29 September 2023
                : 32
                : 66-97
                Affiliations
                [a ]Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
                [b ]Department of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of Korea
                [c ]Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea
                [d ]Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Cambridge, MA, 02139, USA
                [e ]College of Medicine, Korea University, Seoul, 02841, Republic of Korea
                [f ]Department of Biomedical Engineering, University of Illinois, Chicago, IL, 60607, USA
                [g ]Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA
                [h ]Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, 60208, USA
                Author notes
                []Corresponding author. Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. dhkim@ 123456northwestern.edu
                [∗∗ ]Corresponding author. Department of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of Korea. heeminkang@ 123456korea.ac.kr
                [1]

                These authors contribute equally to this work.

                Article
                S2452-199X(23)00298-0
                10.1016/j.bioactmat.2023.09.015
                10562133
                37822917
                e5da8a16-9d05-4fea-bcb2-b7c6fd06066f
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 30 June 2023
                : 6 September 2023
                : 23 September 2023
                Categories
                Review Article

                magnetic nanoparticles,ferroptosis cancer therapy,diagnostic imaging,magnetic resonance imaging,synergistic cancer imaging and therapy

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