Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 8, 2024

Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis maintaining redox balance countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) soybean phospholipid (SP) as pyroptosis promoters (Pd

Язык: Английский

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Metal–Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells

ACS Nano, Год журнала: 2024, Номер 18(19), С. 12386 - 12400

Опубликована: Май 3, 2024

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability produce effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal–organic framework in situ-generate therapeutic vaccination. Once inside early endosome, alkaline overexpressed cells' membrane activates situ type I photodynamic effect of Cu-THBQ/AX for generating •O2–, catalyzes O2 H2O2 •O2– •OH via semiquinone radical catalysis Fenton-like reactions. This surge ROS endosomes triggers caspase-3-mediated proinflammatory pyroptosis activating phospholipase C. Meanwhile, can also induce oligomerization dihydrolipoamide S-acetyltransferase trigger cell cuproptosis. The production could release effectively inhibiting efferocytosis macrophages convert apoptosis cells into secondary necrosis. simultaneous induction pyroptosis, cuproptosis, necrosis converts from "cold" "hot" conditions, making it antigen pool. transformation successfully antitumor response, growth metastasis.

Язык: Английский

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Lactate and lactylation in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Язык: Английский

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Multi‐Enzyme Mimetic MoCu Dual‐Atom Nanozyme Triggering Oxidative Stress Cascade Amplification for High‐Efficiency Synergistic Cancer Therapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер 64(1)

Опубликована: Авг. 22, 2024

Single-atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)-mediated cancer therapy. However, the high energy barriers of reaction intermediates on single-atom sites and overexpressed antioxidants tumor microenvironment restrict amplification oxidative stress, resulting unsatisfactory therapeutic efficacy. Herein, we report a multi-enzyme mimetic MoCu dual-atom nanozyme (MoCu DAzyme) various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared Mo SAzyme, introduction Cu atoms, formation synergetic effects among enhance substrate adsorption reduce barrier, thereby endowing DAzyme stronger Benefiting from above enzyme-like activities, can not only generate multiple ROS, but also deplete GSH block its regeneration to trigger cascade stress. Additionally, strong optical absorption near-infrared II bio-window endows remarkable photothermal conversion performance. Consequently, achieves high-efficiency synergistic treatment incorporating collaborative therapy This work will advance applications DAzymes provide valuable insights for nanocatalytic

Язык: Английский

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Copper-Based Biomaterials for Anti-Tumor Therapy: Recent Advances and Perspectives

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 28, 2025

Noninvasive phototherapy with functional preservation is considered to be a promising cancer therapeutic method. However, the clinical application of tumor severely restrained by lack appropriate multimodal agents exhibiting an ideal tissue penetration depth maximize antitumor efficiency as well maintain important functions. Herein, innovative near-infrared ray (NIR)-triggered photodynamic-photocatalytic-photothermal therapy (PDT-PCT-PTT) agent based on atomically dispersed cobalt single-atom enzyme (Co-SAE) anchored hollow N-doped carbon sphere (HNCS) has been strategically developed. Reactive oxygen species (ROS) are highly activated and amplified through both photogenerated electrons photothermal conversion induced NIR irradiation, systematically demonstrated experimental density theory (DFT) calculation results. Mild hyperthermia eventually achieved apoptosis ferroptosis caused ROS, significantly boosting interaction ROS dynamic effects thermodynamic in microenvironment (TME). More importantly, Co-SAEs/HNCS not only causes damage limited TME products but also preserves organ functions induction mild local hyperthermia. This work expands biomedical field SAEs presents all-in-one, concept for noninvasive treatment head neck cancer. Non-invasive treatment, hindered that have desirable depth. Here, authors report light- triggered sphere.

Язык: Английский

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New horizons for the therapeutic application of nanozymes in cancer treatment

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 20, 2025

The advent of nanozymes has revolutionized approaches to cancer diagnosis and therapy, introducing innovative strategies that address the limitations conventional treatments. Nanozyme nanostructures with enzyme-mimicking catalytic abilities exhibit exceptional stability, biocompatibility, customizable functions, positioning them as promising tools for theranostics. By emulating natural enzyme reactions, can selectively target eradicate cells, minimizing harm adjacent healthy tissues. Nanozymes also be functionalized specific targeting ligands, allowing precise delivery regulated release therapeutic agents, improving treatment effectiveness reducing adverse effects. However, issues such selectivity, regulatory compliance remain critical challenges clinical application nanozymes. This review provides an overview nanozymes, highlighting their unique properties, various classifications, activities, diverse applications in strategic oncological deployment could profoundly impact future advancements personalized medicine, recent progress prospective directions enzyme-mimetic treatment. summarizes

Язык: Английский

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Ultrasmall Enzyodynamic PANoptosis Nano‐Inducers for Ultrasound‐Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition

Advanced Materials, Год журнала: 2024, Номер 36(45)

Опубликована: Сен. 3, 2024

Abstract Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form inflammatory programmed cell death, presents dependable strategy combating cancer by engaging multiple death pathways (apoptosis, pyroptosis, necroptosis). In this study, ultrasmall Bi 2 Sn O 7 nanozyme with ultrasound‐magnified multienzyme‐mimicking properties designed engineered as PANoptosis inducer through destroying mitochondrial function tumor cells enhancing intracellular accumulation toxic reactive oxygen species, finally triggering activation process. The role has been verified expression related proteins, including cleaved Caspase 3, NLRP3, N‐GSDMD, 1, p‐MLKL, RIPK3. inclusion external ultrasonic irradiation significantly augments enzyodynamic efficiency. vitro in vivo antineoplastic efficacy, along inhibition lung metastasis, validate benefits ‐mediated pathway. This study not only elucidates intricate mechanisms underlying inducer, but also offers novel perspective treatment carcinoma.

Язык: Английский

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Nanomaterial-mediated self-calibrating biosensors for ultra-precise detection of food hazards: Recent advances and new horizons

Coordination Chemistry Reviews, Год журнала: 2024, Номер 522, С. 216204 - 216204

Опубликована: Сен. 10, 2024

Язык: Английский

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Portable Colorimetric Sensor Array Based on a Porous Single‐Atom Fe Nanozyme with Different Surface Sites for Identifying Artificially Ripened Fruits

Advanced Functional Materials, Год журнала: 2024, Номер 35(2)

Опубликована: Окт. 4, 2024

Abstract Single‐atom nanozyme materials have demonstrated exceptional specific catalytic activity due to the atomic‐level dispersion of their active centers. However, exploration mechanisms for single‐atom catalysts is so far limited 2D surfaces nanozymes. In this study, porous Fe (psaFeN) successfully prepared through a straightforward coordination‐assisted polymerization‐assembly strategy. The psaFeN composite nanospheres are uniformly sized, exhibiting excellent dispersibility with well‐organized pore channels extending from center surface. Density functional theory calculations reveal that in nanozyme, (010) facets serve as primary surface, where atoms form tri‐coordinated or tetra‐coordinated structures doped nitrogen atoms. (100) act auxiliary reactive Fe─N center. exhibits POD‐like ( K m = 1.77 mM; V max 173.53 × 10 − ⁸ M s −1 ). Given bioactivity, portable colorimetric biosensor constructed distinguishing artificially ripened fruits naturally ones. sensor achieves precise discrimination detection limit low 310 nmol L . This study anticipated offer valuable insights into understanding 3D nanozymes, promoting application development robust biosensors food safety.

Язык: Английский

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