CHEMISTRY OF MATERIALS
·
2024
·
IF 7.2
Xiangjie Tian,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cancer cells is a challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation of CuO2 within mesoporous silica nanoparticles (MSN) and then deposition with a tannic acid (TA)-Cu2+ complex, is designed and developed to realize on-demand copper delivery for cuproptosis-based combination therapy. CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex is readily disassembled to release Cu2+ and liberate the internal CuO2 to produce Cu2+ and H2O2. The overloaded Cu2+ can not only directly convert endogenous H2O2 and self-supplied H2O2 into highly toxic hydroxyl radicals for chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction into Cu+ species to induce potent cellular cuproptosis and enhance CDT. The experimental results indicate that CuO2-MSN@TA-Cu2+ produces remarkable cytotoxicity against cancer cells and significantly suppresses tumor growth by 93.42% in mice-bearing 4T1 breast tumors. This work provides a new paradigm to boost cuproptosis-related therapy and may also inspire the design of advanced therapeutic nanoplatforms.
研究领域:
纳米技术
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癌症生物学
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治疗学
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材料科学
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产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Yuan Ding,Ruohan Chen,Jianfen Zhou,Yanning Bao,Nana Meng,Xudong Zheng,Shengmin Yang,Jiasheng Lu,Zhixuan Jiang,Yu Liu,Cao Xie,Linwei Lu,Weiyue Lu
There remain several intractable challenges for chemotherapy in glioma treatment, including the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and tumor heterogeneity caused by cancer stem cells (CSCs), which are resistant to conventional chemotherapy. Here, we established a nano strategy to kill glioma cells and CSCs, combining carfilzomib and bis(diethyldithiocarbamate)copper. The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis. The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site. This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.
研究领域:
肿瘤学
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药理学
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纳米技术
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yiqun Zhang,Ni Zhang,Jianghao Xing,Yiwei Sun,Xu Jin,Cailiang Shen,Liang Cheng,Yuanyin Wang,Xianwen Wang
Chemodynamic therapy (CDT) involving the use of metal nanozymes presents new opportunities for the treatment of deep-seated tumors. However, the lower ROS catalytic rate and dependence on high H 2 O 2 concentrations affect therapeutic efficacy. To address this issue, a hydrogel was constructed for the treatment of osteosarcoma by combining Cu–Fe 3 O 4 nanozymes (NCs) and artemisinin (AS) coencapsulated in situ with sodium alginate (ALG) and calcium ions. This hydrogel can release nanoparticles and AS within tumor tissue for an extended period of time, utilizing the multienzyme activity of NCs to achieve ROS accumulation. The carbon radicals (•C) generated from the interaction of Fe 2+ /Cu 2+ with AS amplify oxidative stress, leading to tumor cell damage. Simultaneously, the NCs activate ferroptosis via the GPX4 pathway by depleting GSH and activate cuproptosis via the DLAT pathway by causing intracellular copper overload, enhancing therapeutic efficacy. In vitro experiments confirmed that the NCs-AS-ALG hydrogel has an excellent tumor cell killing effect, while in vivo experimental results demonstrated that it can effectively eliminate tumors with excellent biocompatibility , providing a new approach for osteosarcoma treatment.
研究领域:
生物医学工程
·
纳米技术
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肿瘤学
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材料科学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Pengcheng Hu,Yongxin Li,Luchen Zhang,Xiaopeng Lan,Xiaochuan Ren,Wenlong Liang,Shen Wang,Yizhen Wang,Yanhui Zhao,Yanhui Zhang,Chunzhao Liu,Chunlei Liu
Cuproptosis is a newly recognized copper-dependent nonapoptotic form of cell death, which stimulate studies exploring copper-based nanomaterials to treat cancer through distinct mechanistic action. However, it remains a challenge to completely eradicate tumors via monotherapy. Herein, a copper-doped BiSe x (CBS) nanozyme was developed to boost αPD-L1-mediated immune checkpoint blocking (ICB) via synergetic apoptosis/cuproptosis-induced immunogenic cell death (ICD). The defect-engineered CBS nanozyme exhibits strong peroxidase-mimicking activities and generates abundant reactive oxygen species (ROS) production causing cell apoptosis, which could be further augmented by NIR photoirradiation. Meanwhile, the CBS could cause mitochondrial lipoylated protein aggregation, leading to cell cuproptosis. The photothermal/catalytic/cuproprosis synergistic therapy triggered by CBS nanozyme combined with αPD-L1 antibody effectively inhibits the growth of primary tumors and distant tumors in prostate cancer model. Furthermore, CBS nanozyme exhibited significant germicidal effect in wound infection. Collectively, this work provides a new insight into cancer treatment of copper-based nanozyme based on cuproptosis/apoptosis-related combined therapy.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·562
·
IF 15
Chen Chao,Song Songlin,Wu Wenlong,Yu Ningjun,Zheng Chuansheng,Zhou Guofeng,Ren Yanqiao,Dong Xiangjun
Introduction Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC); however, TACE refractoriness remains a major clinical challenge. Increasing evidence suggests that post-embolization hypoxia-driven metabolic reprogramming, particularly dysregulated copper homeostasis, contributes to therapeutic resistance. Objective This study aimed to elucidate the role of copper metabolism in TACE-refractory HCC and to develop a mechanism-driven nanoembolic strategy targeting the copper chaperone ATOX1 to induce cuproptosis and reverse TACE refractoriness. Methods Clinical serum samples from HCC patients with TACE refractoriness or favorable response were analyzed for copper levels and copper transport–related proteins. A thermosensitive nanogel (Cu²⁺/DC_AC50@PNA) co-loaded with copper ions and the ATOX1 inhibitor DC_AC50 was synthesized and characterized. Its embolic performance, antitumor efficacy, and biosafety were evaluated in rabbit renal artery and VX2 orthotopic liver tumor models. In vitro assays using Huh-7 and LM3 cells under normoxic and hypoxic conditions assessed cell viability, migration, invasion, and cuproptosis-related signaling. Results Patients with TACE refractoriness exhibited significantly elevated serum copper levels and increased ATOX1 and ATP7B expression, indicating systemic copper dyshomeostasis. Cu²⁺/DC_AC50@PNA demonstrated favorable physicochemical properties, sustained embolic capability, and excellent biocompatibility. In vivo, this nanoembolization system markedly suppressed tumor growth, increased tumor necrosis, reduced metastasis, and prolonged survival compared with conventional cTACE. Mechanistically, Cu²⁺/DC_AC50@PNA disrupted intracellular copper transport, activated cuproptosis, inhibited HIF-1α/VEGF-mediated angiogenesis, and remodeled the tumor immune microenvironment by enhancing CD8⁺ T-cell infiltration. In vitro findings corroborated potent antitumor and anti-metastatic effects, particularly under hypoxic conditions. Conclusion Copper metabolism dysregulation is a defining feature of TACE-refractory HCC. Targeting ATOX1-mediated copper homeostasis using Cu²⁺/DC_AC50@PNA represents a novel and effective strategy to induce cuproptosis, overcome TACE refractoriness, and improve therapeutic outcomes in HCC. Graphical
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Yi Hu,Zijian Hu,Yuting Ding,Yuan Zhou,Duo Zhou,Song Ye,Wei Jiang,Yanbin Zhang,Junhui Song,Chengying Meng,Yu Chen,Yueyang Fang,Mengran Xu,Yexiang Sun,Xu-Lin Chen,Delin Hu
Protease-armed GCP breaks EPS barriers for deep biofilm penetration. • NIR-boosted copper overload drives cuproptosis-like bacterial killing. • GCP amplifies ROS generation through peroxidase-like nanozyme activity. • GCP eradicates mature biofilms and prevents new biofilm formation. • GCP promotes early M1 defense and late M2 repair in infected wounds. Biofilm infections are notoriously difficult to eradicate because the EPS matrix limits drug penetration and the local immune environment often fails to clear pathogens, leading to chronic inflammation and delayed healing. Here, we present a protease-armed copper nanozyme–antibiotic platform, Gen@CuS@BSA/protease (GCP), designed to integrate biofilm disruption, copper-overload–mediated killing, and stage-adaptive immunoregulation under near-infrared (NIR) activation. GCP incorporates alkaline protease to degrade EPS and create diffusion channels, CuS-based photothermal heating to enhance copper uptake and induce copper-overload-associated, cuproptosis-like bacterial killing, and peroxidase-like activity to amplify oxidative stress in the presence of H₂O₂, thereby boosting antibacterial efficacy. In vitro , GCP robustly eradicated established P. aeruginosa PAO1 biofilms and inhibited biofilm formation, consistent with improved intrabiofilm penetration. Transcriptomic analysis and RT–qPCR revealed suppression of central carbon metabolism and virulence- and biofilm-associated pathways, supporting a copper-driven lethal mechanism. In an infected wound model, GCP with NIR accelerated bacterial clearance and wound closure. Notably, GCP outperformed the protease-free counterpart (GC) in modulating macrophage dynamics—promoting early M1 activation for antibacterial defense while facilitating a subsequent M2 shift to resolve inflammation and support tissue remodeling. This study provides a unified strategy for treating refractory biofilm infections by synchronizing deep penetration, cuproptosis-like killing, and immuno-regenerative healing. Download: Download high-res image (336KB) Download: Download full-size image
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DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaoyuan Yi,Huaying Xie,Kunzhao Huang,Jianzhang Luo,Wen Li,Qingyu Zeng,Feifei He,Wuxiang Shi,Duo Wang,Liyan Wang
Activating a robust immune response is an effective strategy for achieving tumor eradication. In this study, copper-based metal-organic framework nanoparticles (referred to as FA-PZ@MOF NPs), which have the ability to simultaneously induce cuproptosis and pyroptosis in tumor cells, were designed to utilize the synergistic effects of cuproptosis and pyroptosis to trigger immunogenic cell death (ICD). This can inhibit tumor growth, migration, and metastasis while enabling efficient antitumor immunotherapy. The nano inducer targets hepatocellular carcinoma tumor cells via folic acid, dissociates and releases copper ions in the tumor microenvironment (TME), which has a high glutathione concentration, leading to copper ion overload, thereby mediating cuproptosis. Additionally, the released ZnO 2 generates substantial amounts of H 2 O 2 and Zn 2+ in the acidic environment, enhancing the Cu 2+ -based Fenton-like reaction for chemokinetic therapy. This exacerbates the reactive oxygen species (ROS) storms and mitochondrial damage, and combined with the action of Polyphyllin VI (PPVI), induces pyroptosis and cuproptosis. This multilayered interaction strategy also triggers robust ICD while inhibiting hepatocellular carcinoma tumor metastasis and invasion.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Zhen Guo,Renlu Han,Yun Gao,Jie Fu,Zekai Zhuang,Yafei Hou,Jiancheng Yu,Keqi Tang
Abnormal metabolic symbiosis is one of the most typical features of tumors that distinguishes them from normal tissues. Disrupting tumor metabolic symbiosis has been recognized a promising tumor therapeutic approach. However, a single pathway intervention strategy greatly impedes its treatment efficiency. Herein, α-cyano-4-hydroxycinnamic acid (CHCA) and elesclomol (ES) co-loaded Cu 7 S 4 nanoplatform (named as CCE) is developed to synchronously intervene tricarboxylic acid (TCA) cycle and lactic acid metabolism through self-enhanced cuproptosis and acidosis for tumor metabolic symbiosis destruction. CCE could be triggered by up-regulated glutathione (GSH) in cancer cells to release ES, CHCA, Cu ions, and S 2− ions. On the one hand, ES significantly improves the influx efficiency of Cu ions to mitochondria where cuproptosis is initiated and TCA cycle is attacked. Meanwhile, the H 2 S produced by the binding of S 2− to H + in acidic tumor cells could induce mitochondrial damage and inhibit Cu ions efflux by depriving energy supply. Moreover, the GSH consumption reduces its chelation with Cu ions. Collectively, the increased intracellular Cu ions level significantly boosts cuproptosis mediated proteotoxicity of TCA cycle, thus aggravating TCA cycle injury. On the other hand, CHCA down-regulates the expression of monocarboxylate transporters 4 (MCT4) and inhibits lactic acid transport between tumor cells, causing the tumor cytoplasm acidification. Interestingly, H 2 S accelerates lactate production by promoting the glucose uptake to further potent the lactate metabolic disorder. In vitro and in vivo experiments confirm anti-tumor efficacy and biosafety of CCE. This study further enriches tumor therapeutic strategy.
研究领域:
肿瘤生物学
·
代谢调控
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生物化学
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产品关联
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Hui Wang,Weitao Yang,Yan Xu,Weiwei Zeng,Dinghua Liu,Tianming Cui,Yanjing Yun,Chang Liu,Zhuoyao Wu,Bingbo Zhang
Monovalent copper (Cu(I)) drives cuproptosis and catalytic therapy, yet its rapid oxidation reduces the activity. We developed bioinspired Cu(I)-bovine serum albumin single-atom nanozymes (Cu(I)-BSA SAzymes) via mild biomineralization, achieving stability (>90 days) and dual enzyme-like activities (peroxidase (POD)/catalase (CAT)) to convert tumor H2O2 into cytotoxic reactive oxygen species (ROS) while alleviating hypoxia. These SAzymes deplete glutathione to amplify oxidative stress and release Cu(I), which aggregates dihydrolipoamide S-acetyltransferase (DLAT) to induce cuproptosis─distinct from apoptosis/ferroptosis. Mechanistically, transcriptomics analyses suggest that Cu(I)-BSA SAzymes exerted their effects by regulating the oxidative stress and energy metabolism in 4T1 cells. The tumor microenvironment further mediates SAzymes aggregation and in situ transformation into paramagnetic Cu(II), enabling self-amplified T1-weighted MRI contrast for real-time activation monitoring. In breast (4T1) and colon (CT26) tumors, Cu(I)-BSA SAzymes suppress growth by 68.8% and 80.3% ([Cu] = 4 mg kg–1). This study reports a stable Cu(I) platform for catalytic-plus-cuproptosis theranostics.
研究领域:
肿瘤学
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纳米医学
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生物材料
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分子影像
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氧化应激
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细胞死亡机制
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-18
·
IF 52.7
Yue Yan,Li Shuoyuan,Su Qiang,Wan Xufeng,Li Qiaochu,Zhang Zhuang,Xu Hong,Zheng Fuyuan,Zhang Yangming,Tong Le,Cao Jian,Zhao Long,Chen Xiaoting,Li Qi,Zeng Yi,Wang Haoyang,Deng Yi,Zhou Zongke,Wang Duan
Conventional antibiotic strategies often fail to consistently suppress escaping planktonic bacteria and even induce antibiotic resistance, allowing implant-associated infections (IAIs) to persist. In this study, we demonstrated an antibiotic-free coating engineered with an herbal bioheterojunction featuring a shell-in-shell structure where Cu 2 O forms the core, strontium (Sr) is loaded in the inner shell, and curcumin (Cur) is nucleated in situ at the outer heterointerface (Cu 2 O-Sr/Cur). Ultrasound-triggered reactive oxygen species (ROS) generation by the outer heterostructure (Cu 2 O/Cur), coupled with Cu(I)-induced cuproptosis-like bacterial death, achieved antibacterial rates of 99.56% against S. aureus and 99.43% against E. coli . When ultrasonication ceases, the released Cu(I) undergoes disproportionation reactions to form Cu(II), which can chelate with Cur to form Cu-Cur metal complexes. These complexes exhibit enhanced antioxidative properties through self-catalytic regulation, the scavenging of ROS, and the activation of anti-inflammatory M2 macrophage phenotype. Moreover, strontium release from the inner shell simultaneously suppressed osteoclast activity and promoted osteogenesis, resulting in trabecular number and thickness increases of 129.03% and 56.71%, respectively, compared with those in control group. Therefore, our work establishes a sequential treatment strategy for the antibacterial properties and osteointegration ability of IAIs.
研究领域:
生物医学工程
·
抗菌材料
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纳米医学
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生物材料
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感染控制
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骨组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Bin Liu,Xiaorui Chen,Yanlin Zhu,Hao Chen,Jia Tan,Zhuang Yang,Jing Li,Pan Zheng,Lili Feng,Qingqing Wang,Shili Gai,Lei Zhong,Piaoping Yang,Ziyong Cheng,Jun Lin
To improve the efficiency and application prospects of metal peroxides in tumor therapy, the synthesis of bimetallic peroxides via simple yet effective approaches will be highly significant. In this work, hyaluronic acid modified zinc-copper bimetallic peroxides (ZCPO@HA) nanoparticles are synthesized through a one-step symbiotic method by co-hydrolysis of zinc acetate and copper acetate in weakly alkaline solution, followed by modification with sodium hyaluronate. Upon decomposition in the tumor microenvironment, ZCPO@HA nanoparticles can generate a considerable content of hydroxyl radical (·OH) by Fenton-like reaction between Cu 2+ and self-compensating hydrogen peroxide, while downregulating the expression of glutathione peroxidase 4 to induce ferroptosis. The abundant release of Cu 2+ leads to the aggregation of dihydrolipoamide S-acetyltransferase and the reduction of iron-sulfur cluster proteins, causing cuproptosis. The immunogenic cell death of tumor cells releases abundant damage associated molecular patterns, effectively activating the adaptive immune response. Zn 2+ and ·OH cause mitochondrial damage, leading to the release of a substantial amount of mitochondrial DNA. This subsequently activates the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway, enhancing the innate immune response. In conclusion, it synthesizes a new type of bimetallic peroxides by one-step symbiosis for activating anti-tumor immunotherapy combined with immune checkpoint inhibitor.
研究领域:
生物化学
·
肿瘤学
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免疫学
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产品关联
DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2025
·Vol. 31
·期 34
·109825
·
IF 5.4
Peng-Tuo Xiao,Chang-Feng Li,Yuan-Da Liu,Jing Zhong,Xi-Lun Cui,Chang Liu,Wei Yang
BACKGROUND Colorectal cancer (CRC) is a major global health burden. B cell CLL/lymphoma 10 (BCL10), a key component of the caspase recruitment domain protein-BCL10-mucosa-associated lymphoid tissue lymphoma paracaspase complexes, is upregulated in CRC and associated with poor patient prognosis, suggesting its potential role in CRC development and progression. Cuproptosis, a novel form of programmed cell death, has emerged as a promising therapeutic strategy for cancer. AIM To explore the role of BCL10 in regulating the sensitivity of CRC cells to cuproptosis. METHODS A series of in vitro and in vivo experiments were conducted using CRC cell lines and CRC mouse models to evaluate the effects of BCL10 on CRC cell proliferation, migration, invasion, and sensitivity to copper-induced cell death. Mechanistic studies were performed to elucidate the underlying molecular pathways. RESULTS BCL10 promoted CRC cell proliferation, migration, and invasion, while its knockdown had the opposite effects. BCL10 also influenced the sensitivity of CRC cells to cuproptosis, with BCL10 overexpression enhancing resistance and its knockdown increasing sensitivity. The mechanism involved BCL10 modulating the expression of DLAT, a key protein in the copper-induced cell death pathway, through activation of the nuclear factor kappa-B (NF-κB) signaling pathway. CONCLUSION BCL10 promotes CRC growth and regulates the sensitivity of CRC cells to cuproptosis by activating the NF-κB signaling pathway and modulating DLAT expression. These findings provide a molecular basis for developing BCL10-targeted therapies for CRC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
信号转导
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转化医学
·
癌变机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）