Cuproptosis and copper as potential mechanisms and intervention targets in Alzheimer's disease

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117814 - 117814

Published: Jan. 13, 2025

Language: Английский

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Biometallic ions and derivatives: a new direction for cancer immunotherapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 15, 2025

Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become breakthrough treatment, achieving good efficacy wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as tolerance escape. (e.g. zinc, copper, magnesium, manganese, etc.) can assist enhancing through activation cells, enhancement tumor antigen presentation, improvement microenvironment. addition, biometallic derivatives directly inhibit cell progression offer possibility effectively overcoming limitations current by promoting responses reducing immunosuppressive signals. This review explores potential application prospects immunotherapy, providing new ideas for future clinical metal part helping to guide development more effective safe therapeutic regimens.

Language: Английский

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Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy

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

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Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 28, 2024

Language: Английский

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Polyvalent Aptamer Nanodrug Conjugates Enable Efficient Tumor Cuproptosis Therapy Through Copper Overload and Glutathione Depletion

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(44), P. 30033 - 30045

Published: Oct. 28, 2024

Cuproptosis, a recently identified form of copper-dependent cell death, shows promising tumor suppressive effects with minimal drug resistance. However, its therapeutic efficacy is hampered by dependence on copper ions and the glutathione (GSH)-rich microenvironment in tumors. Here, we have developed polyvalent aptamer nanodrug conjugates (termed CuPEs@PApt) nucleosome-like structure to improve cuproptosis therapy exploiting mitochondrial overload GSH depletion. Polyvalent (PApt), comprising epithelial adhesion molecule aptamers for targeting repetitive PolyT sequences chelation, facilitates efficient loading targeted delivery peroxide-Elesclomol nanodots (CuPEs). Upon internalization cells, Elesclomol released from CuPEs@PApt accumulates mitochondria initiate cuproptosis, while lysosomal degradation CuP generates exogenous Cu2+ H2O2, triggering Fenton-like reaction depletion enhance cuproptosis. In vitro vivo experiments confirm this strategy inducing immunogenic latter contributing activation antitumor immune response synergistic growth inhibition.

Language: Английский

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SRF/SLC31A1 signaling promotes cuproptosis induced by celastrol in NSCLC

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114165 - 114165

Published: Jan. 27, 2025

Language: Английский

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Single-atom–doped piezocatalyst induces copper-free cuproptosis in tumor therapy

Science Advances, Journal Year: 2025, Volume and Issue: 11(7)

Published: Feb. 14, 2025

Cuproptosis, a distinct cell death pathway, has been integrated into nanomedicine for disease theranostics. However, current nanosystems inducing cuproptosis rely on exogenous toxic copper ions, limiting the scope of biomaterials. Developing nanoplatforms that induce without holds substantial promise. Here, we engineered two-dimensional iron (Fe) single-atom–doped molybdenum disulfide (MoS 2 ) piezocatalyst (Fe-MoS tumor therapy. Incorporating single Fe atoms enhances MoS piezoelectric polarization via charge redistribution and modulates Mo oxidation states, enabling multifaceted enzymatic activities, including peroxidase-, glutathione oxidase–, oxidase-, catalase-like activities. Upon ultrasound stimulation, Fe-MoS nanocatalyst generates reactive oxygen species depletes synergistic piezocatalytic enzyocatalytic effects, disrupting ion homeostasis cuproptosis, concurrently triggering ferroptosis ferritinophagy, which collectively suppression. This study represents first paradigm to introduce copper-free initiating substantially advancing applications in

Language: Английский

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Zinc-copper bimetallic nanoplatforms trigger photothermal-amplified cuproptosis and cGAS-STING activation for enhancing triple-negative breast cancer immunotherapy

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

Published: Feb. 24, 2025

Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and recurrence, along with a low sensitivity to immunotherapy, resulting in paucity effective therapeutic strategies. Herein, we have developed polydopamine-coated zinc-copper bimetallic nanoplatforms (Cu-ZnO2@PDA nanoplatforms, abbreviated CZP NPs) that can efficiently induce photothermal amplified cuproptosis cGAS-STING signaling pathway activation, thereby reversing the immunosuppressive tumor microenvironment TNBC, upregulating PD-L1 expression, boosting efficacy anti-programmed death-ligand 1 antibody (αPD-L1)-based immunotherapy. Within acidic (TME), NPs spontaneously release copper zinc ions hydrogen peroxide, generating highly oxidative hydroxyl radicals downregulating iron-sulfur cluster proteins. These actions lead disruption mitochondrial integrity, DNA (mtDNA) irreversible cuproptosis. The further synergy between mtDNA potentiates activation pathway, triggering robust antitumor immune response sensitizing TNBC αPD-L1 therapy. Additionally, using an 808 nm near-infrared laser for therapy significantly augments these effects, cascade amplification against TNBC. strategic combination markedly bolsters immunity suppresses growth. Collectively, our findings present promising synergistic strategy treatment linking cuproptosis, therapy,

Language: Английский

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Injectable celastrol-loading emulsion hydrogel for immunotherapy of low-immunogenic cancer

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

Published: March 6, 2025

Immunotherapy, exemplified by immune checkpoint blockade (ICB), has been extensively employed in antitumor treatments. Nevertheless, its efficacy addressing low-immunogenic tumors not yielded satisfactory results, primarily due to the depletion and inadequate infiltration of effector T cells within tumor microenvironment (TME). Here, we construct an injectable water-in-oil emulsion hydrogel load clinically used Celastrol (Gel@Cel), which addresses limitations Cel's hydrophobicity. Cel can both inhibit cell proliferation promote apoptosis, while simultaneously inducing immunogenic death, through activation AKT MAPK pathways. In a model refractory hepatocellular carcinoma with malignant ascites, intraperitoneal administration Gel@Cel significantly inhibits progression activates effects lipase-controlled release Cel, as compared free Cel. Intriguingly, induces dendritic cells, resulting cytotoxic TME ascites. Furthermore, increases expression programmed death protein ligand-1 (PD-L1) cells. Moreover, combining PD-1 antibody (αPD-1) further enhances effect amplifies activation. conclusion, exhibits promising therapeutic potential treatment tumors, especially when combined ICB therapy.

Language: Английский

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Functional nanozyme system for synergistic tumor immunotherapy via cuproptosis and ferroptosis activation

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

Published: March 15, 2025

Elevated copper levels induce tumor cuproptosis and ferroptosis, leading to immunogenic cell death subsequent antitumor immune responses. However, dysregulated metabolism in cells maintains homeostatic balance, while hypoxic microenvironments hinder therapeutic efficacy. In this study, we present a nanozyme system, termed CussOMEp, comprising copper-based nanovector (CussNV) that is PEGylated loaded with omeprazole, transporter inhibitor, enhance synergistic immunotherapy by promoting ferroptosis. CussNV assembled from dithiodiglycolic acid ions, exhibiting peroxidase, glutathione oxidase, catalase-like activities, along responsive degradability. This alleviates hypoxia producing oxygen, induces ferroptosis through the generation of lethal hydroxyl radicals, depletes glutathione. Additionally, omeprazole increases cellular concentration oxidative stress inhibiting intracellular copper-transporting ATPase 1 (ATP7A), enhancing lipoylated protein oligomerization cuproptosis. breast mouse model, CussOMEp elicits robust responses, including dendritic maturation T proliferation. When combined PD-1 antibodies (αPD-1), significantly inhibits metastasis bilateral lung metastatic models. work presents functional system as promising strategy for leveraging

Language: Английский

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