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      The application of nanoparticles-based ferroptosis, pyroptosis and autophagy in cancer immunotherapy

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          Abstract

          Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.

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          Most cited references285

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          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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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
                chenyuan55@126.com
                tangsk1990@163.com
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                7 March 2024
                7 March 2024
                2024
                : 22
                : 97
                Affiliations
                [1 ]GRID grid.412793.a, ISNI 0000 0004 1799 5032, Department of Urology, , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, ; Wuhan, 430030 China
                [2 ]GRID grid.412793.a, ISNI 0000 0004 1799 5032, Department of Geriatric Medicine, , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, ; Wuhan, 430030 China
                Article
                2297
                10.1186/s12951-024-02297-8
                10921615
                38454419
                ef165d7b-8e67-4d3b-82ae-840ae775d2dd
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 April 2023
                : 2 January 2024
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: No.81900645
                Award ID: No.82170779
                Award ID: No.82270804
                Funded by: the Natural Science Foundation of Hubei Province
                Award ID: No.2021CFB366
                Funded by: 2019 Wuhan Yellow Crane Talent Program (Outstanding Young Talents), the Tongji Hospital (HUST) Foundation for Excellent Young Scientist
                Award ID: No.2020YQ15
                Funded by: Young Elite Scientists Sponsorship Program by CAST
                Award ID: No.YESS20220646
                Funded by: Hainan Provincial Natural Science Foundation of China
                Award ID: No.823MS177
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Biotechnology
                ferroptosis,pyroptosis,autophagy,nanomaterials,cancer immunotherapy
                Biotechnology
                ferroptosis, pyroptosis, autophagy, nanomaterials, cancer immunotherapy

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