Heliyon
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2024
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IF 3.4
Rujun Chen,Yating Huang,Ke Sun,Fuyun Dong,Xiaoqin Wang,Junhua Guan,Lina Yang,He Fei
Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in “Lymphatic Invasion” and “Cancer status” were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.
研究领域:
肿瘤学
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生物信息学
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分子生物学
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PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Jinyue Sun,Han-Xiao Zhuang,Jia-Neng Pan,Qian-Jun Shen,Hui-Ling Shen,Wen-Wen Zhou
This study has investigated cuproptosis caused by copper sulfate (CuSO 4 ) in Escherichia coli O157: H7 and its mechanism. Meanwhile, the mechanism of CuSO 4 combined with natamycin (Nata) against E. coli O157: H7 planktonic and biofilm cells were also investigated. Finally, we prepared an agar-based film, researched its properties, and used it for packaging cherry tomatoes and purple kale. The results indicated that CuSO 4 could cause cuproptosis in E. coli O157: H7 and lead the genes related to Fe-S cluster protein ( hyfA , sufB , xdhC , and narY ) to down-regulate and cuproptosis-related proteins to change. Then, CuSO 4 combined with Nata could synergistically decrease E. coli O157: H7 bacterial counts in planktonic condition and biofilm by synergistically affecting the membrane potential, cytoplasm leakage, permeability of outer membrane and inner membrane. After that, CuSO 4 and Nata could change the mechanical properties, color and optical characteristics of agar-based film, and decrease the water vapor permeability and oxygen permeability value. Finally, CuSO 4 @Nata@Carboxymethylcellulose@Agar film effectively lowered the counts of E. coli O157: H7 in cherry tomatoes and purple kale during the storage.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Wenqian Zheng,Yang Liu,Jinru Liu,Yuping Zhao,Peiyu Wang,Yi Wang,Yuxuan Wang,Zeyu Lu,Xiaofan Liu,Yaru Shi,Na Zhou,Fermín Eduardo González,Hongchen Sun,Ding Zhou,Xiaowei Xu
Squamous cell carcinoma remains a highly aggressive malignancy with persistently high global incidence and mortality rates, posing significant challenges for effective treatment. Traditional chemotherapies lack specificity, leading to damage in normal tissues and severe side effects, highlighting the urgent need for targeted therapeutic strategies. In this study, copper and calcium co-doped carbon dots (Cu/Ca-CDs) were synthesized using a vacuum-confined heating method. These Cu/Ca-CDs demonstrated excellent tumor-targeting ability through specific binding to folate receptors on murine squamous cell carcinoma cell line (SCC7), facilitated by their pterin ring structure. Mechanistic studies revealed that Cu/Ca-CDs induced SCC7 tumor cell death through copper-induced cuproptosis and calcium overload-mediated apoptosis, as confirmed by Western blot, immunofluorescence staining, and Rhod-2 calcium probe analyses. The dual-mode imaging capability of Cu/Ca-CDs, enabled by fluorescence and computed tomography properties, allowed for real-time tracking of their distribution and accumulation within tumors. This imaging-guided approach ensured precise delivery to tumor tissues while minimizing damage to normal tissues. In vivo experiments demonstrated significant tumor volume reduction and increased survival rates in tumor-bearing mice treated with Cu/Ca-CDs, without any observed toxicity to normal tissues or changes in body weight, underscoring the efficacy and biosafety of Cu/Ca-CDs. These findings highlight Cu/Ca-CDs as a promising strategy for precision oncology, offering effective tumor targeting, dual-mode imaging, and synergistic anti-tumor efficacy with reduced side effects.
研究领域:
肿瘤学
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医学影像学
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材料科学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Chongqing Yu,Qiqi Lu,Yichun Wang,Zujiang Liu,Sathishkumar Gnanasekar,Ugo D’Amora,En-Tang Kang,Liqun Xu,Jie Xu,Xi Rao
Methicillin-resistant Staphylococcus aureus (MRSA) wound infections remain a significant global challenge and demand new-generation biomaterials to eliminate bacterial infections and promote rapid wound healing. Although the nanozyme is a promising approach, the restricted unimodal bactericidal functionality hinders its efficacy in treating complex wound infections. In this study, copper-tannic acid (Cu-TA) nanozymes (NMs) with multifunctional properties were developed for the treatment of bacterial infections and biofilms via cuproptosis-like cell death. The as-prepared Cu-TA demonstrated peroxidase-like (POD-like) activity, generating substantial amounts of hydroxyl radicals (•OH). In vitro studies revealed that Cu-TA efficiently disrupted bacterial biofilms, while in vivo experiments demonstrated its ability to promote anti-inflammatory responses, angiogenesis, collagen synthesis, and cellular proliferation. Transcriptome sequencing revealed that bacterial reactive oxygen species (ROS) caused damage to the cell membrane and disrupted metabolic processes. Furthermore, copper overload triggered lipid peroxidation (LPO) buildup and interfered with the tricarboxylic acid (TCA) cycle, culminating in cuproptosis-like bacterial death. Overall, this study successfully developed a spindle-shaped, multifunctional nanozyme for combating bacterial infections through cuproptosis-like cell death while promoting infected wound healing. The results validate the clinical potential of Cu-TA NMs for treating MRSA-infected wounds.
研究领域:
生物材料学
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纳米医学
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感染与免疫
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2022
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IF 5.738
Li Jinfei,Chen Shuangyi,Liao Yuxuan,Wang Hongyi,Zhou Dawei,Zhang Bo
Background: Metastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.Methods: Thirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.Result: Arecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.Conclusion: We found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2026
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IF 5.4
Yanghao Hu,Jiali He,Pengfei Liu,Yanqi Huang,Da Li,Junlei Liu,Zihao Xia,Hongshuai Liu,Wenying Li,Zhisen Shen
The integration of novel regulatory pathways for cell death with conventional chemotherapy provides a new approach for cancer treatment. Therefore, we constructed a self-assembled nano drug platform (CuT@DOC) by combining a copper-based metal-organic framework (CuT) and docetaxel (DOC), aiming to synergistically enhance the inhibitory effect on laryngeal squamous cell carcinoma (LSCC). The CuT@DOC has been confirmed to have a unique “sphere-sheet” hybrid morphology, high stability, and efficient drug loading through a series of structural characterizations. In addition, the CuT@DOC catalyze strong ROS generation and glutathione depletion under tumor-mimicking acidic and H₂O₂-rich environments. Therefore, the CuT@DOC significantly enhanced oxidative stress via continuous Cu²⁺/Cu⁺ cycling, amplifying ROS accumulation and triggering cuproptosis. Concurrently, DOC preserved its microtubule-targeting function, inducing pronounced G2/M arrest. The integration of these mechanisms led to synergistic cytotoxicity against LSCC cells, with markedly reduced toxicity in normal fibroblasts and epithelial cells. The CuT@DOC also exhibited superior therapeutic efficacy and selectivity, underscoring the advantage of combining chemotherapy with copper-dependent cell death in a single nanoplatform. This work proposes CuT@DOC as a robust and biocompatible nanoplatform that leverages dual mechanisms cuproptosis and microtubule disruption to achieve potent and selective tumor inhibition. This study will provide experimental and theoretical support for multimodal nanotherapeutic strategies, offering a promising direction for the precision treatment of LSCC and potentially broader head and neck malignancies.
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DOI
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Cong Tang,Kairui Liu,Xiaoning Gao,Hanmeixuan Kang,Weijie Xie,Jin Chang,Linling Yin,Jun Kang
Cuproptosis is an emerging form of programmed cell death and shows enormous prospect in cancer treatment. Excessive generation of reactive oxygen species (ROS), metal ion accumulation, and the tricarboxylic acid (TCA) cycle collapse are pivotal elements in the triggering of cell death via mitochondrial pathways. Herein, a cascade nanoreactor CaCuZC has been constructed by incorporating nanosonosensitizer IR780 carbon dots (IR780 CD) and calcium peroxide (CaO 2 ) into metal-organic frameworks (MOF) for synergistic cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Within tumor cells, CaCuZC dissociates into CaO 2 , Cu 2+ and sonosensitizer IR780 CD. The decomposition of CaO 2 could generate H 2 O 2 to strengthen the Cu 2+ -based chemodynamic therapy and Ca 2+ overload induces amplified intracellular oxidative stress, thus leading to mitochondrial dysfunction. As a result, the combination of Cu 2+ and Ca 2+ overload together induce cascade mitochondrial damage. Moreover, the sonosensitizer IR780 CD generates ROS under ultrasound irradiation to amplify intracellular oxidative stress. In addition, the overloaded Cu 2+ released from CaCuZC leads to the aggregation of lipoylated protein dihydrolipoamide S-acetyltransferase, thus resulting in cuproptosis. Furthermore, ferroptosis could been concomitantly induced by CaCuZC with intracellular glutathione (GSH) consumption and lipid peroxidation (LPO) accumulation. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. CaCuZC enhances the infiltration and activation of tumor-specific cytotoxic T cells to transform a “cold” tumor into a “hot” tumor, activating the anti-tumor immune response. This study provides a cascade of mitochondrial damage strategy for triggering cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy and achieving improved therapeutic effects. Statement of significance To improve the efficacy of tumor immunotherapy, a cascade nanoreactor CaCuZC was successfully constructed based on a self-assembly strategy for cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Upon decomposition within the acidic and GSH-overexpressing tumor microenvironment, CaCuZC released CaO 2 and Cu 2+ and sonosensitizer IR780 CD. The CaO 2 further produced H 2 O 2 /O 2 and Ca 2+ in a weakly acidic environment to strengthen the Cu 2+ -based CDT and IR780 CD-mediated SDT, respectively. The overload copper ions not only led to cuproptosis, but also efficiently induced ferroptosis. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. This study presents a cascade of mitochondrial damage strategy for cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy.
研究领域:
癌症研究
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纳米技术
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治疗学
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免疫学
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生物化学
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DOI
PubMed
高影响因子
Biomaterials Research
·
2026
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IF 9.8
Xinru Shen,Ying Zhang,Mengyan Shan,Yiqing Kou,Xintao Jia,Mengru Yang,Changxiang Yu,Jingbai Li,Pan Guo,Jiawei Li,Zhidong Liu
Triple-negative breast cancer (TNBC) presents formidable treatment barriers due to dysfunctional vasculature and an immunosuppressive microenvironment. To address these challenges, we engineered a bioinspired near-infrared (NIR)-responsive copper–polyphenol nanoplatform, SCP, to implement a NIR-triggered “bridge-and-attack” therapeutic strategy. This nanoassembly was constructed through the coordination of salvianolic acid B (SAB) with copper ions and further stabilized by a polydopamine (PDA) shell. Upon NIR irradiation, SAB and Cu 2+ were co-released from SCP, enabling simultaneous vascular remodeling and tumor cell killing. The released SAB promoted vascular normalization, increasing pericyte coverage to 51.6% and alleviating tumor hypoxia, thereby facilitating intratumoral penetration and immune-cell infiltration. Meanwhile, released Cu 2+ , together with PDA-mediated photothermal activation, induced cuproptosis and immunogenic cell death (ICD). This combined remodeling of the tumor microenvironment enhanced CD8 + T cell infiltration and achieved a tumor inhibition rate of 88.5% in 4T1 tumor-bearing mice with favorable systemic biosafety. Overall, this interfacial nanomaterial design integrates vascular normalization, photothermal-enhanced cuproptosis, and immunotherapy, providing a promising materials-based strategy for TNBC treatment.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
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IF 9.9
Zheng Yang,Zhou Zhao,Hanlong Cheng,Yuhua Shen,Anjian Xie,Manzhou Zhu
Multimodal combined therapy (MCT) is an emerging avenue to eliminate tumor cells by the synergistic effect of various therapeutic methods. However, the complex tumor microenvironment (TME) is becoming the key barrier to the therapeutic effect of MCT due to the excessive existence of H + ions, H 2 O 2 , and glutathione (GSH), the lack of O 2 , and the relaxation of ferroptosis. To overcome these limitations, smart nanohybrid gels with excellent biocompatibility, stability and targeting function were prepared by using gold nanoclusters as cores and an in situ cross-linking composite gel of sodium alginate (SA)/hyaluronic acid (HA) as the shell. The obtained Au NCs-Cu 2+ @SA-HA core–shell nanohybrid gels possessed near-infrared light response synergistically benefitting photothermal imaging guided photothermal therapy (PTT) and photodynamic therapy (PDT). Meanwhile, the H + -triggered release of Cu 2+ ions from the nanohybrid gels not only induces cuproptosis to avoid the relaxation of ferroptosis, but also catalyzes H 2 O 2 in the TME to generate O 2 to simultaneously improve the hypoxic microenvironment and PDT effect. Furthermore, the released Cu 2+ ions could consume the excessive GSH to form Cu + ions effectively, which caused the formation of hydroxyl free radicals (·OH) to kill tumor cells, synergistically realizing GSH consumption-enhanced PDT and chemodynamic therapy (CDT). Hence, the novel design in our work provides another research avenue for cuproptosis-enhanced PTT/PDT/CDT via TME modulation.
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PubMed
高影响因子
Materials Today Bio
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2026
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IF 11
Hui Zhang,Xu Zhu,Jingchun Wang,Yibo Huo,Yikai Ma,Shengzhong Rong,Yuting Lu,Yingxue Jin
To address the core issue of low clinical response rates (10%-30%) to α-PD-L1 immune checkpoint blockade therapy, this study targeted the immunosuppressive bottleneck mediated by lactate accumulation in the tumor microenvironment (TME). A targeted drug delivery system (HLC) was constructed using hyaluronic acid (HA) nanomicelles co-loaded with lactate oxidase (LOX) and copper-doped carbon dots (CuCDs). Combined with α-PD-L1, a synergistic antitumor strategy integrating lactate metabolic regulation, cuproptosis, and immune activation was established. HLC achieves targeted accumulation through specific binding between HA and CD44 receptors on tumor cells. It directionally releases LOX and CuCDs in the acidic TME via pH-responsive properties. LOX efficiently clears lactate and elevates pH, blocking the HIF-1α/PD-L1 pathway to reverse immunosuppression. It also generates H 2 O 2 in situ to provide substrates for Cu-mediated Fenton-like reactions, enhancing cuproptosis. In vitro experiments confirm that HLC promotes dendritic cell maturation and drives M2-type macrophage polarization toward the M1 phenotype. In vivo studies using CT26 tumor-bearing mouse models show that HLC combined with 808 nm laser and α-PD-L1 significantly inhibits primary and distant tumor growth. It remodels the antitumor immune microenvironment with favorable biosafety. This study elucidates the synergistic mechanism between lactate metabolic regulation and cuproptosis, establishes an association between lactate level and cuproptosis sensitivity, and provides a novel strategy and experimental basis for combined cancer immunotherapy with important clinical translation value.
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PubMed
高影响因子
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