Disulfidptosis: a new target for central nervous system disease therapy

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 5, 2025

Disulfidptosis is a pathologic process that occurs under conditions of NADPH deficiency and excess disulfide bonds in cells express high levels SLC7A11. This caused by glucose deprivation-induced stress was first described cancer researchers. Oxidative hypothesized mechanism underlying diseases the central nervous system (CNS), specific type oxidative stress. Proteins linked to disulfidptosis metabolic pathways involved are significantly associated with CNS (neurodegenerative disease, neurogliomas ischemic stroke). However, responsible for this correlation remains unknown. review provides comprehensive overview current knowledge regarding origin elements, genetic factors, signaling proteins pathogenesis disulfidptosis. It demonstrates disruption thiometabolism play critical roles diseases, which potential role We also summarize disulfidptosis-related drugs highlight therapeutic strategies treating diseases. Additionally, paper suggests testable hypothesis might be promising target

Язык: Английский

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Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cells can develop resistance through the SLC7A11-GSH-GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, with high become vulnerable to disulfidptosis under glucose-deprived conditions. We aimed dual-mode strategy that simultaneously induces ferroptosis by targeting both lipid peroxidation glucose metabolism in cells. Fe-Cu-SS metal-organic frameworks (MOFs) loaded BAY876 (FCSP@876 MOFs) were synthesized enhance trigger The MOFs characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV-Vis spectroscopy. In vitro experiments demonstrated FCSP@876 reactive oxygen species (ROS) levels while depleting NADPH. Western blotting actin filament staining confirmed underlying mechanisms. vivo xenograft BALB/c mice assessed synergistic effects of induction. During induction, exhibited an adaptive upregulation expression. effectively counteracted this mechanism inducing restricting uptake BAY876, leading NADPH depletion subsequent disulfidptosis. Both enhanced efficacy compared single-mode treatments. This study successfully developed novel combines MOFs, offering overcoming therapy.

Язык: Английский

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NIR-Activated Hollow Upconversion Nanocomposites for Tumor Therapy via GLUT1 Inhibition and Mitochondrial Function Disruption

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Tumor remains a leading contributor to global mortality rates, necessitating urgent advancements in therapeutic interventions. Due the intricate nature of tumor microenvironment, individual differences make it difficult achieve desired efficacy with single strategy. To overcome these challenges, we develop for first time hollow NaBiF4-based nanocomposites NaBiF4-W/R-D therapy by glucose transporter 1 (GLUT1) inhibition and mitochondrial function disruption. can inhibit GLUT1 due presence WZB117, which leads decrease intracellular cells, leaving them starved state. Meanwhile, upconversion luminescence under near-infrared (NIR) laser irradiation stimulate photosensitizer efficiently generate singlet oxygen disrupt then kill cells. In addition, NIR-II emission from is used fluorescence imaging determine optimal point treatment. Finally, membrane potential depolarization, impaired function, activation caspase-3, ultimately amplification apoptosis.

Язык: Английский

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Zinc phthalocyanine and sulfasalazine coloaded nanoaggregates with Prussian blue functionalization for sensitizing tumor photothermal/photodynamic therapy

Journal of Colloid and Interface Science, Год журнала: 2025, Номер 685, С. 509 - 521

Опубликована: Янв. 14, 2025

Язык: Английский

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Nanoenhanced‐Cuproptosis Results From the Synergy of Calcium Overload and GSH Depletion with the Increasing of Intracellular Ca/Mn/Cu Ions

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Abstract Cuproptosis is a newly discovered copper‐dependent form of cell death. Intracellular glutathione (GSH) acts as copper chelator to inhibit cuproptosis, so the reduction GSH concentration conducive enhancing cuproptosis cells. In order reduce content and interfere with mitochondrial metabolism, strategy based on calcium overload depletion enhance proposed in this study. Containing manganese (Mn) (Cu) elements, CaCO 3 nanoparticles (NPs) are modified MCF‐7 aptamer (CaCO /Mn/Cu@lip‐Apt). When entering cell, /Mn/Cu@lip‐Apt decomposed released Mn* (Mn 2+ /Mn 3+ 4+ ), Cu Ca . The high valence Mn ion can effectively consume produce which catalyzed H 2 O reactive oxygen species (ROS), while reducing concentration. production ROS promoted influx exogenous large accumulation led intracellular overload, resulting dysfunction metabolism disorders. , turn triggered cuproptosis. This showed excellent antitumor effects provided new way study disease treatment.

Язык: Английский

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Nebulized M2 macrophage-derived nanovesicles for the treatment of explosion-induced acute lung injury

Journal of Colloid and Interface Science, Год журнала: 2025, Номер unknown, С. 137381 - 137381

Опубликована: Март 1, 2025

Язык: Английский

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Synchronously Evoking Disulfidptosis and Ferroptosis via Systematical Glucose Deprivation Targeting SLC7A11/GSH/GPX4 Antioxidant Axis

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Disulfidptosis and ferroptosis are recently identified programmed cell deaths for tumor therapy, both of which highly depend on the intracellular cystine/cysteine transformation cystine transporter solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (SLC7A11/GSH/GPX4) antioxidant axis. However, disulfidptosis usually asynchronous due to opposite effect transport them. Herein, systematic glucose deprivation, by inhibiting upstream uptake promoting downstream consumption, is proposed synchronously evoke ferroptosis. As an example, Au nanodots Fe-apigenin (Ap) complexes coloaded FeOOH nanoshuttles (FeOOH@Fe-Ap@Au NSs) employed regulate SLC7A11/GSH/GPX4 axis performing disulfidptosis- ferroptosis-mediated therapy synchronously. In this scenario, exhibit oxidase-like activity when consuming massive glucose. Meanwhile, Ap can inhibit downregulating 1, depriving fundamentally. The systematical deprivation limits supplement NADPH suppresses axis, thus solving contradiction addition, efficient delivery exogenous iron ions FeOOH@Fe-Ap@Au NSs self-supplied H2O2 through nanodots-catalytic oxidation facilitate Fenton reaction therewith help amplify a result synchronous occurrence ferroptosis, good efficacy in ovarian cancer therapeutic model.

Язык: Английский

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A heterojunction-engineering nanodrug with tumor microenvironment responsiveness for tumor-specific cuproptosis and chemotherapy amplified sono-immunotherapy

Biomaterials, Год журнала: 2025, Номер 321, С. 123319 - 123319

Опубликована: Апрель 4, 2025

Язык: Английский

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Disulfidptosis

Current Biology, Год журнала: 2025, Номер 35(7), С. R241 - R243

Опубликована: Апрель 1, 2025

Язык: Английский

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Upgrading the Bioinspired Iron-Polyporphyrin Structures by Abiological Metals Toward New-Generation Reactive Oxygen Biocatalysts

Nano Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 27, 2024

Developing artificial enzymes based on organic molecules or polymers for reactive oxygen biocatalysis has broad applicability. Here, inspired by heme-based enzyme systems, we construct the abiological iron group metal-based polyporphyrin (Ru/Os-coordinated porphyrin-based biocatalyst, Ru/Os-PorBC) to serve as a new generation of efficient and versatile species (ROS)-related biocatalyst. Due structural benefits, including excellent electron configuration, appropriate bandgap, optimized adsorption activation reaction intermediates, Ru/Os-PorBC shows unparalleled ROS-production activities regarding maximum rate turnover numbers, which also demonstrates superior pH temperature adaptability compared natural enzymes. Impressively, Os-PorBC manifests most efficacious capabilities, surpassing not only Ru/Fe-PorBC but existing state-of-the-art ROS-related Our findings provide pivotal direction developing next-generation polyporphyrin-based biocatalysts, setting stage era upgrading metalloenzymes metals.

Язык: Английский

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