Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications DOI Creative Commons
Y. Cong, Na Li, Zixin Zhang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.

Language: Английский

Tumor Microenvironment Responsive Hollow Nanoplatform for Triple Amplification of Oxidative Stress to Enhance Cuproptosis‐Based Synergistic Cancer Therapy DOI Open Access
Weijun Xu, Yaping Wang,

Guanghui Hou

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(13)

Published: Jan. 30, 2023

Cuproptosis is a recently discovered form of programmed cell death and shows great potential in cancer treatment. Herein, copper-dithiocarbamate chelate-doped artemisinin-loaded hollow nanoplatform (HNP) developed via chelation competition-induced hollowing strategy for cuproptosis-based combination therapy. The HNP exhibits tumor microenvironment-triggered catalytic activity, wherein liberated Cu2+ catalyzes artemisinin endogenous H2 O2 to produce C-centered radicals hydroxyl radicals, respectively. Meanwhile, the disulfide bonds-rich can deplete intracellular glutathione, thus triply amplifying oxidative stress. augmented stress sensitizes cells cuproptosis, causing prominent dihydrolipoamide S-acetyltransferase oligomerization mitochondrial dysfunction. Moreover, activate ferroptosis inhibiting GPX4 activity trigger apoptosis dithiocarbamate-copper chelate-mediated ubiquitinated proteins accumulation, resulting potent antitumor efficacy. Such cuproptosis/ferroptosis/apoptosis synergetic opens new avenue

Language: Английский

Citations

64
Mechanisms and regulations of ferroptosis DOI Creative Commons

Xu-Dong Zhang,

Zhongyuan Liu,

Mao-Sen Wang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

Regulation of cell mortality for disease treatment has been the focus research. Ferroptosis is an iron-dependent regulated death whose mechanism extensively studied since its discovery. A large number studies have shown that regulation ferroptosis brings new strategies various benign and malignant diseases. Iron excess lipid peroxidation are primary metabolic features. Therefore, genes involved in iron metabolism can regulate overload through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) body’s non-enzymatic antioxidants plays a pivotal role struggle against peroxidation. GSH functions as auxiliary substance peroxidase 4 (GPX4) to convert toxic peroxides their corresponding alcohols. Here, we reviewed researches on recent years, comprehensively analyzed regulatory process from metabolism, then described detail GPX4 main antioxidant vivo .

Language: Английский

Citations

56
The copper age in cancer treatment: From copper metabolism to cuproptosis DOI
Wensheng Xie, Zhenhu Guo,

Lingyun Zhao

et al.

Progress in Materials Science, Journal Year: 2023, Volume and Issue: 138, P. 101145 - 101145

Published: May 23, 2023

Language: Английский

Citations

48
Copper homeostasis and cuproptosis in mitochondria DOI

Ziying Tian,

Su Jiang,

Jieyu Zhou

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

Citations

48
Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application DOI Open Access
Na Liu,

Min‐Bin Chen

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116115 - 116115

Published: Jan. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

Language: Английский

Citations

47
Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy DOI
Sheng Lü, Yifan Li, Yingjie Yu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Language: Английский

Citations

46
Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy DOI Creative Commons
Yang Zhu,

Xuegang Niu,

Chengyu Ding

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 6, 2024

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based

Language: Английский

Citations

42
Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia DOI
Yuting Huang, Xueliang Liu, Jiawei Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13805 - 13816

Published: March 29, 2024

Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity suppresses body's antitumor response. Herein, we have successfully immobilized functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing conversion H2O2 O2, thereby sensitizing Meanwhile, increased oxygenation expression hypoxia-inducible factor-1 (HIF-1) protein, resulting in alleviation immunosuppressive microenvironment. Of note, induces immunogenic (ICD), which facilitates dendritic (DC) maturation antigen presentation polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation cells complements checkpoint blockers (αPD-L1), enhancing immunity. strategy cuproptosis-mediated responses alleviating hypoxia effectively promotes activation proliferation effector T cells, ultimately leading long-term immunity against cancer.

Language: Английский

Citations

38
Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis DOI

Guanzhong He,

Yongchun Pan,

Fei Zeng

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(12), P. 9031 - 9042

Published: March 12, 2024

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting acid-degradable copper hydride (CuH) nanoparticles was developed via microfluidic synthesis. After coating tumor-targeting hyaluronic acid (HA), denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. can induce apoptosis relying on Fenton-like reactions lead to causing mitochondrial protein aggregation. Besides, existence H2 enhance both cell death types dysfunction intracellular redox homeostatic disorders. In vivo experimental results further exhibit desirable potential HCP for killing inhibiting lung metastases, which will broaden horizons designing materials triggering better efficacy.

Language: Английский

Citations

30
Recent advances in molecular mechanisms of skin wound healing and its treatments DOI Creative Commons
Abdullah Al Mamun, Chuxiao Shao, Peiwu Geng

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 21, 2024

The skin, being a multifaceted organ, performs pivotal function in the complicated wound-healing procedure, which encompasses triggering of several cellular entities and signaling cascades. Aberrations typical healing process wounds may result atypical scar development establishment persistent condition, rendering patients more vulnerable to infections. Chronic burns have detrimental effect on overall quality life patients, resulting higher levels physical discomfort socio-economic complexities. occurrence frequency prolonged are rise as aging people, hence contributing escalated expenditures within healthcare system. clinical evaluation treatment chronic continue pose challenges despite advancement different therapeutic approaches. This is mainly owing duration intricate processes involved wound healing. Many conventional methods, such administration growth factors, use dressings, application skin grafts, used ease across diverse types. Nevertheless, these approaches only be practical for some wounds, highlighting need advance alternative modalities. Novel care technologies, nanotherapeutics, stem cell treatment, 3D bioprinting, aim improve efficacy, prioritize regeneration, minimize adverse effects. review provides an updated overview recent advancements management using innovative

Language: Английский

Citations

29