Cuproptosis-Inducing Functional Nanocomposites for Enhanced and Synergistic Cancer Radiotherapy DOI

Tiaoyan Jiang,

Tian-Ying Jia,

Yipengchen Yin

и другие.

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Radiotherapy is crucial in local cancer management and needs advancements. Tumor cells elevate intracellular copper levels to promote growth resist radiation; thus, targeted delivery mitochondria could enhance radiotherapy by inducing cuproptosis tumor cells. In this study, we engineered a multifunctional nanoliposome complex, termed Lipo-Ele@CuO2, which encapsulates both peroxide (CuO2) the chelator elesclomol, can Cu ions mitochondria. The Lipo-Ele@CuO2 complex induces mitochondria-mediated synergistically enhances efficacy of radiotherapy. CuO2 acts as donor exhibits inherent sensitivity acidic environments. Additionally, it depletes glutathione, thereby sensitizing cuproptosis. Leveraging its pH-responsive properties microenvironment, facilitate controlled release efficiently delivering at sites. combined vitro vivo studies demonstrate that Lipo-Ele@CuO2-based therapy significantly improves antitumor excellent safety profiles, effectively boosting effectiveness Furthermore, metabolomic transcriptomic analyses reveal combination precipitates significant alterations energy metabolism, notably repressing genes related iron-sulfur cluster assembly glycolysis, confirming induction This therapeutic strategy provides viable approach for addressing clinical resistance demonstrates translational potential.

Язык: Английский

The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions DOI Open Access
Guang Lei, Li Zhuang, Boyi Gan

и другие.

Cancer Cell, Год журнала: 2024, Номер 42(4), С. 513 - 534

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

126
Diverse functions of cytochrome c in cell death and disease DOI
Zhuan Zhou, Tasnim Arroum, Xu Luo

и другие.

Cell Death and Differentiation, Год журнала: 2024, Номер 31(4), С. 387 - 404

Опубликована: Март 23, 2024

Язык: Английский

Процитировано

52
Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer DOI Creative Commons

Lei Ma,

Chong Chen,

Chunxing Zhao

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 7, 2024

Abstract Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player immunotherapy-related resistance. Ferroptosis, form cell death driven by iron-dependent lipid peroxidation, highly regulated cellular metabolism remolding and has shown to synergistic effects when combined with immunotherapy. Metabolic adaption CSCs drives tumor resistance, yet mechanisms their ferroptosis defense evasion remain elusive. Here, through metabolomics, transcriptomics, epithelial-specific Cpt1a -knockout mouse model, clinical analysis, we demonstrate that CPT1A, key rate-limiting enzyme fatty acid oxidation, acts L-carnitine, derived from tumor-associated macrophages drive ferroptosis-resistance CD8 + T inactivation Mechanistically, CPT1A restrains ubiquitination degradation c-Myc, while c-Myc transcriptionally activates expression. The CPT1A/c-Myc positive feedback loop further enhances antioxidant capacity activating NRF2/GPX4 system reduces amount phospholipid polyunsaturated acids ACSL4 downregulating, thereby suppressing CSCs. Significantly, targeting blockade-induced anti-tumor immunity tumoral tumor-bearing mice. results illustrate potential mechanism-guided therapeutic strategy metabolic vulnerability improve efficacy cancer

Язык: Английский

Процитировано

42
Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis DOI Creative Commons

Shimeng Zhou,

Junlan Liu, Andi Wan

и другие.

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Апрель 23, 2024

Abstract Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action various physical, chemical and biological factors. The exploration tumorigenesis mechanism crucial for early prevention treatment tumors. Epigenetic modification common important in cells, including DNA methylation, histone modification, non-coding RNA m6A modification. mode cell death programmed by death-related genes; however, recent researches have revealed some new modes death, pyroptosis, ferroptosis, cuproptosis disulfidptosis. regulation deaths mainly involved key proteins affects up-regulating or down-regulating expression levels proteins. This study aims to investigate epigenetic modifications regulating disulfidptosis tumor explore possible triggering factors development microscopic point view, provide potential targets therapy perspective antitumor drugs combination therapies.

Язык: Английский

Процитировано

34
Exploiting ferroptosis vulnerabilities in cancer DOI
Toshitaka Nakamura, Marcus Conrad

Nature Cell Biology, Год журнала: 2024, Номер 26(9), С. 1407 - 1419

Опубликована: Июнь 10, 2024

Язык: Английский

Процитировано

31
Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death DOI Creative Commons
Lei Sun, Wenwen Shao, Zhiheng Lin

и другие.

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 5, 2024

Язык: Английский

Процитировано

26
Exploring new perspectives in immunology DOI Creative Commons
Ruslan Medzhitov, Akiko Iwasaki

Cell, Год журнала: 2024, Номер 187(9), С. 2079 - 2094

Опубликована: Апрель 1, 2024

Several conceptual pillars form the foundation of modern immunology, including clonal selection theory, antigen receptor diversity, immune memory, and innate control adaptive immunity. However, some immunological phenomena cannot be explained by current framework. Thus, we still do not know how to design vaccines that would provide long-lasting protective immunity against certain pathogens, why autoimmune responses target antigens others, or response infection sometimes does more harm than good. Understanding these mysteries may require question existing assumptions develop test alternative explanations. Immunology is increasingly at a point when, once again, exploring new perspectives becomes necessity.

Язык: Английский

Процитировано

20
Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications DOI Creative Commons
Yongxin Zheng, Junlu Sun,

Zhiting Luo

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(11)

Опубликована: Ноя. 26, 2024

Abstract Regulated cell death (RCD) refers to the form of that can be regulated by various biomacromolecules. Each modalities have their distinct morphological changes and molecular mechanisms. However, intense evidences suggest lipid peroxidation common feature initiates propagates death. Excessive alters property membrane further damage proteins nucleic acids, which is implicated in human pathologies. Here, we firstly review classical chain process peroxidation, clarify current understanding myriad roles mechanisms RCD types. We also discuss how involves diseases such intimate association between peroxidation-driven leveraged develop rational therapeutic strategies.

Язык: Английский

Процитировано

19
The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy DOI Creative Commons
Meike Vogler, Yannick Braun, Victoria M. Smith

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 21, 2025

Abstract The B cell lymphoma 2 (BCL2) protein family critically controls apoptosis by regulating the release of cytochrome c from mitochondria. In this cutting-edge review, we summarize basic biology BCL2 including canonical and non-canonical functions, highlight milestones research to clinical applications in cancer other pathophysiological conditions. We review laboratory development BH3-mimetics as well more recent approaches proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) tools BH4 domain BCL2. first BCL2-selective BH3-mimetic, venetoclax, showed remarkable efficacy with manageable toxicities has transformed treatment several hematologic malignancies. Following its success, chemically similar inhibitors such sonrotoclax lisaftoclax are currently under evaluation, alone combination. Genetic analysis highlights importance BCL-X L MCL1 across different types possible utility these proteins. However, or been challenging, on-target thrombocytopenia for cardiac precluding development. Tumor-specific inhibition may be achieved novel using PROTACs selective drug delivery strategies would transformational many subtypes malignancy. Taken together, envision that proteins, while already a success story translational research, foreseeable future have broader applicability improve multiple diseases.

Язык: Английский

Процитировано

5
PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products DOI Creative Commons

Chuanxiang Zhao,

Shan Lin

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

The intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents gut microbiota from lamina propria within resident mucosal immune cells to maintain homeostasis. is manifested contiguous monolayer of specialized epithelial (IEC), interconnected through tight junctions (TJs). integrity this paramount. Consequently, excessive IEC death advances permeability consequence thereof translocation bacteria into propria, subsequently triggering an inflammatory response, which underpins clinical disease trajectory bowel (IBD). A burgeoning body evidence illustrates landscape where undergoes several model programmed cell (PCD) pathophysiology pathogenesis IBD. Apoptosis, necroptosis, pyroptosis represent principal modalities PCD with intricate specific pathways molecules. Ample has revealed substantial mechanistic convergence crosstalk among these three aforementioned forms death, expanding conceptualization PANoptosis orchestrated by PNAoptosome complex. This review provides concise overview molecular mechanisms apoptosis, pyroptosis. Furthermore, based on between deaths IEC, details current knowledge regarding regulation natural products. Our objective broaden comprehension innovative underlying IBD furnish foundation for developing more drugs treatment IBD, benefiting both practitioners research workers.

Язык: Английский

Процитировано

3