Cellular Trojan Horse initiates bimetallic Fe-Cu MOF-mediated synergistic cuproptosis and ferroptosis against malignancies

Science Advances, Journal Year: 2024, Volume and Issue: 10(15)

Published: April 10, 2024

Disruptions in metal balance can trigger a synergistic interplay of cuproptosis and ferroptosis, offering promising solutions to enduring challenges oncology. Here, we have engineered Cellular Trojan Horse, named MetaCell, which uses live neutrophils stably internalize thermosensitive liposomal bimetallic Fe-Cu MOFs (Lip@Fe-Cu-MOFs). MetaCell instigate thereby enhancing treatment efficacy. Mirroring the characteristics neutrophils, evade immune system not only infiltrate tumors but also respond inflammation by releasing therapeutic components, surmounting traditional barriers. Notably, Lip@Fe-Cu-MOFs demonstrate notable photothermal effects, inciting targeted release Fe-Cu-MOFs within cancer cells amplifying action ferroptosis. has demonstrated outcomes tumor-bearing mice, effectively eliminating solid forestalling recurrence, leading extended survival. This research provides great insights into complex between copper iron homeostasis malignancies, potentially paving way for innovative approaches treatment.

Language: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 647 - 647

Published: Feb. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Language: Английский

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Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

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

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Associations between patterns of blood heavy metal exposure and health outcomes: insights from NHANES 2011–2016

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 22, 2024

Abstract Background Extensive research has explored the association between heavy metal exposure and various health outcomes, including malignant neoplasms, hypertension, diabetes, heart diseases. This study aimed to investigate relationship patterns of a mixture seven metals these outcomes. Methods Blood samples from 7,236 adults in NHANES 2011–2016 studies were analyzed for levels cadmium, manganese, lead, mercury, selenium, copper, zinc. Cluster analysis logistic regression identified three distinct mixed exposure, their associations with outcomes evaluated. Results Pattern 1 exhibited higher odds ratios (ORs) malignancy during 2011–2012 (OR = 1.33) 2015–2016 1.29) compared pattern 2. 3 showed lower OR 2013–2014 0.62). For displayed ORs than 2 1.26), 1.31), 1.41). had hypertension 0.72) 0.67). In terms diseases, 1.34), 1.76), 1.68). diseases 0.59) 0.52). However, no significant trend was observed diabetes. All strongest among studied. Conclusions The seven-metal mixtures robust. correlations disease, 2, suggesting an interaction metals. Particularly, could offer valuable insights into management healthy populations.

Language: Английский

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Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27496 - e27496

Published: March 1, 2024

Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism cuproptosis are closely linked in the context of human diseases, with particular focus on cancer. Cuproptosis refers specific type copper-mediated cell death or copper toxicity triggered by disruptions within cells. This phenomenon encompasses spectrum mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum perturbations metal ion equilibrium. Mechanistically, is driven binding lipoylated enzymes tricarboxylic acid (TCA) cycle. interaction participates protein aggregation proteotoxic ultimately culminating death. Targeting its associated pathways cancer cells holds therapeutic potential selectively targeting eliminating cancerous Strategies modulate levels, enhance excretion, interfere cuproptotic being explored identify novel targets for therapy improve patient outcomes. Understanding relationship between malignancies remains an active area research. review provides comprehensive overview association metabolism, homeostasis, cancers, explicitly emphasizing mechanism implications pathogenesis. Additionally, we emphasize aspects treatment.

Language: Английский

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Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: Sept. 17, 2021

Copper (Cu) plays a pivotal role in cancer progression by acting as co-factor that regulates the activity of many enzymes and structural proteins cells. Therefore, Cu-based complexes have been investigated novel anticancer metallodrugs are considered complementary strategy for currently used platinum agents with undesirable general toxicity. Due to high failure rate increased cost new drugs, there is global drive towards repositioning known drugs treatment recent years. Disulfiram (DSF) first-line antialcoholism drug clinics more than 65 yr. In combination Cu, it has shown great potential an targeting wide range cancers. The reaction between DSF Cu ions forms copper diethyldithiocarbamate complex (Cu(DDC) 2 also CuET) which active, potent ingredient through inhibition NF-κB ubiquitin-proteasome system well alteration intracellular reactive oxygen species (ROS). Importantly, DSF/Cu inhibits several molecular targets related resistance, stemness, angiogenesis metastasis thus overcoming tumour recurrence relapse patients. Despite its excellent efficacy, proven unsuccessful clinical trials. This likely due poor stability, rapid metabolism and/or short plasma half-life oral version inability form Cu(DDC) at relevant concentrations tissues. Here, we summarize scientific rationale, targets, mechanisms action cells outcomes ± We will focus on insights harnessing immune hypoxic microenvironment using discuss emerging delivery strategies can overcome shortcomings DSF-based therapies provide opportunities translation or into therapeutics.

Language: Английский

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Interference between copper transport systems and platinum drugs

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 76, P. 173 - 188

Published: May 29, 2021

Language: Английский

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Relationship between copper and immunity: The potential role of copper in tumor immunity

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Nov. 7, 2022

Copper is an essential trace element in organism, and changes copper levels vivo often indicate a diseased state. immunity have been discussed since the last century, with deficiency significantly affecting development function of immune system, such as increased host susceptibility to various pathogens, decreased number impaired neutrophils, reduced antibacterial activity macrophages, proliferation splenocytes, B cell ability produce antibodies cytotoxic T lymphocyte helper cells. In past 20 years, some studies shown that ions are related many tumors, including lung cancer, acute lymphoid leukaemia, multiple myeloma other wherein ion were elevated, current reveal involved development, growth metastasis tumors through pathways. Moreover, recent can regulate expression PD-L1, thus, attention should be paid important role tumor immunity. By exploring studying immunity, new insights into could generated novel therapeutic approaches improve clinical prognosis patients provided.

Language: Английский

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Cuprotosis Programmed-Cell-Death-Related lncRNA Signature Predicts Prognosis and Immune Landscape in PAAD Patients

Cells, Journal Year: 2022, Volume and Issue: 11(21), P. 3436 - 3436

Published: Oct. 31, 2022

In terms of mortality and survival, pancreatic cancer is one the worst malignancies. Known as a unique type programmed cell death, cuprotosis contributes to tumor growth, angiogenesis, metastasis. Cuprotosis programmed-cell-death-related lncRNAs (CRLs) have been linked PAAD, although their functions in microenvironment prognosis are not well understood. This study included data from TCGA-PAAD cohort. Random sampling PAAD was conducted, splitting into two groups for use training set test (7:3). We searched differentially expressed genes that were substantially using univariate Cox Lasso regression analysis. Through multivariate proportional risk regression, risk-rating system developed. Correlations between CRL signature clinicopathological characteristics, microenvironment, immunotherapy response, chemotherapy sensitivity further evaluated. Lastly, qRT-PCR used compare expression healthy tissues tumors. Some CRLs thought strong correlations with outcomes. These include AC005332.6, LINC02041, LINC00857, AL117382.1. The CRL-based construction exhibited outstanding predictive performance offers fresh approach evaluating pre-immune effectiveness, paving way future studies precision immuno-oncology.

Language: Английский

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Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(43)

Published: Oct. 17, 2022

Copper is an essential metal nutrient for life that often relies on redox cycling between Cu(I) and Cu(II) oxidation states to fulfill its physiological roles, but alterations in cellular status can lead imbalances copper homeostasis contribute cancer other metalloplasias with metal-dependent disease vulnerabilities. Copper-responsive fluorescent probes offer powerful tools study labile pools, most of these reagents target Cu(I), limited methods monitoring owing potent fluorescence quenching properties. Here, we report activity-based sensing strategy turn-on, state-specific detection through metal-directed acyl imidazole chemistry. binding a receptor accommodates the harder Lewis acidity relative activates pendant dye reaction proximal biological nucleophiles concomitant ion release, thus avoiding quenching. Copper-directed 649 (CD649.2) provides foundational information existence regulation including identifying divalent transporter 1 (DMT1) as importer, increases response oxidative stress induced by depleting total glutathione levels, reciprocal accompanied decreases oncogenic mutations promote stress.

Language: Английский

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