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      Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

      1 , 2 , 1 , 1 , 2 , 1 , 2
      Small Methods
      Wiley

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          Abstract

          Programmed cell death (PCD, mainly including apoptosis, necrosis, ferroptosis, pyroptosis, and autophagy) and immunogenic cell death (ICD), as important cell death mechanisms, are widely reported in cancer therapy, and understanding the relationship between the two is significant for clinical tumor treatments. Considering that vast nanodrugs are developed to induce tumor PCD and ICD simultaneously, in this review, the interrelationship between PCD and ICD is described using nanomedicines as examples. First, an overview of PCD patterns and focus on the morphological differences and interconnections among them are provided. Then the interrelationship between apoptosis and ICD in terms of endoplasmic reticulum stress is described by introducing various cancer treatments and the recent developments of nanomedicines with inducible immunogenicity. Next, the crosstalk between non-apoptotic (including necrosis, ferroptosis, pyroptosis, and autophagy) signaling pathways and ICD is introduced and their relationship through various nanomedicines as examples is further illustrated. Finally, the relationship between PCD and ICD and its application prospects in the development of new ICD nanomaterials are summarized. This review is believed to deepen the understanding of the relationship between PCD and ICD, extend the biomedical applications of various nanodrugs, and promote the progress of clinical tumor therapy.

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          Most cited references185

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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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            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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              Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin

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                Author and article information

                Contributors
                Journal
                Small Methods
                Small Methods
                Wiley
                2366-9608
                2366-9608
                May 2023
                January 27 2023
                May 2023
                : 7
                : 5
                Affiliations
                [1 ] State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 China
                [2 ] School of Applied Chemistry and Engineering University of Science and Technology of China Hefei 230026 China
                Article
                10.1002/smtd.202201406
                976ce7c4-1831-4566-978b-df1e5cba1d43
                © 2023

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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