Modulation of Metal Homeostasis for Cancer Therapy DOI

Ying Yang,

Huanhuan Fan, Zijian Guo

et al.

ChemPlusChem, Journal Year: 2024, Volume and Issue: 89(6)

Published: Feb. 7, 2024

Metal ions such as iron, zinc, copper, manganese, and calcium are essential for normal cellular processes, including DNA synthesis, enzyme activity, signaling, oxidative stress regulation. When the balance of metal homeostasis is disrupted, it can lead to various pathological conditions, cancer. Thus, understanding role in cancer has led development anti-tumor strategies that specifically target imbalance. Up now, diverse small molecule-based chelators, ionophores, complexes, metal-based nanomaterials have been developed restore metals or exploit dysregulation therapeutic purposes. They hold great promise inhibiting tumor growth, preventing metastasis, enhancing effectiveness existing therapies. In this review, we aim provide a comprehensive summary employed modulate therapy. Their modulation mechanisms succinctly described, their recent applications field therapy discussed. At end, limitations these approaches addressed, potential avenues future developments explored.

Language: Английский

Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors DOI Open Access

Luying Qiao,

Guo‐Qing Zhu, Tengfei Jiang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

Citations

83
Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

Citations

82
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

37
Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy DOI
Guo‐Qing Zhu, Man Wang,

Luying Qiao

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(29)

Published: Feb. 23, 2024

Abstract Autophagy, a lysosome‐involved degradation pathway, as self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for first time, biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported cancer immunotherapy via lysosomal rupture‐mediated “Broken Window Effect”. Only injection Cu‐LDH single therapeutic agent achieves various organelles destruction after rupture, well abnormal aggregation Cu in cells cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by rupture improves overload‐mediated pyroptosis blocking lysosome‐mediated bulk leading to good anti‐tumor immune responses ultimately high‐efficiency growth inhibition. This Effect” provides new paradigm enhanced therapy.

Language: Английский

Citations

23
Cuproptosis: unveiling a new frontier in cancer biology and therapeutics DOI Creative Commons

Ying Feng,

Zhibo Yang,

Jianpeng Wang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

Language: Английский

Citations

19
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives DOI Creative Commons
Chenliang Zhang, Tingting Huang, Liping Li

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Language: Английский

Citations

18
Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy DOI
Guo‐Qing Zhu, Yulin Xie, Junrong Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(45)

Published: Sept. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Language: Английский

Citations

17
Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy DOI
Yuanying Yang, Chen Dong, Xuehua Ma

et al.

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review discusses the recent developments in copper-based nanomaterials that utilize copper-induced cell death, categorized by materials systems, while highlighting limitations of current cuproptosis related nanomaterials.

Language: Английский

Citations

2
Dual Metal Nanoflower Oxygen Pump Microneedles Based on Cuproptosis and STING Pathway Activation for Cancer Immunotherapy DOI Open Access

Jiaojiao Tao,

Yu Dong, Bingjie Wang

et al.

Small, Journal Year: 2025, Volume and Issue: 21(11)

Published: Feb. 14, 2025

Abstract Immunotherapy is a promising new approach for tumor treatment. However, its clinical application hindered by insufficient immunogenicity, hypoxia, and immunosuppressive microenvironment (TME). Here, oxygen pump microneedles (OPMNs) loaded with zinc‐doped copper sulfide nanoflowers (ZCS NFs) PD‐L1 small interfering RNA (siPD‐L1) (OPMNs‐ZCS@siPD‐L1) are developed boosting immunotherapy. OPMN‐ZCS@siPD‐L1 enhances immunogenicity through ZCS NFs inducing cuproptosis, reverses TME siPD‐L1, promotes drug penetration, ameliorates hypoxia bubbles. More importantly, cuproptosis‐induced mitochondrial DNA (mtDNA) together Zn 2+ co‐activate the STING pathway, triggering robust immune response. increases sensitivity to cuproptosis induces immunogenic cell death (ICD) in vivo vitro, which significantly inhibits progression metastasis. The novel strategy of “increasing throttle” (cuproptopsis‐mediated activation & ICD effect) combined “releasing brake” (PD‐L1 inhibition improvement) provides enhancing percutaneous

Language: Английский

Citations

2
Nanoenabled Intracellular Metal Ion Homeostasis Regulation for Tumor Therapy DOI Creative Commons
Lihua Xu,

Mingzheng Peng,

Tingting Gao

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(7)

Published: Dec. 8, 2023

Abstract Endogenous essential metal ions play an important role in many life processes, especially tumor development and immune response. The approval of various metallodrugs for therapy brings more attention to the antitumor effect ions. With deepening understanding regulation mechanisms ion homeostasis vivo, breaking intracellular becomes a new means inhibit proliferation cells activate Diverse nanomedicines with loading small molecular regulators or have been developed disrupt cells, higher safety efficiency than free compounds. This comprehensive review focuses on latest progress regulation‐based including calcium (Ca 2+ ), ferrous (Fe cuprous (Cu + managanese (Mn zinc (Zn ). physiological functions processes are summarized guide design nanomedicines. Then ions‐based some efficient synergistic therapies highlighted. Finally, challenges future developments also discussed, hoping provide reference finding effective therapies.

Language: Английский

Citations

37