Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(29)

Опубликована: Фев. 23, 2024

Abstract Autophagy, a lysosome‐involved degradation pathway, as self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for first time, biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported cancer immunotherapy via lysosomal rupture‐mediated “Broken Window Effect”. Only injection Cu‐LDH single therapeutic agent achieves various organelles destruction after rupture, well abnormal aggregation Cu in cells cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by rupture improves overload‐mediated pyroptosis blocking lysosome‐mediated bulk leading to good anti‐tumor immune responses ultimately high‐efficiency growth inhibition. This Effect” provides new paradigm enhanced therapy.

Язык: Английский

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Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy

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

Опубликована: Сен. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Язык: Английский

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Succinate Nanomaterials Boost Tumor Immunotherapy via Activating Cell Pyroptosis and Enhancing MHC-I Expression

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Despite the promising clinical applications of immunotherapy, its effectiveness is often limited by low immune responses and tumor escape. In this study, we introduce a simple drug-free inorganic nanomaterial, sodium succinate (C4H4Na2O4 NPs), prepared using rapid microemulsion method to enhance cancer immunotherapy. The synthesized C4H4Na2O4 NPs can release high concentrations Na+ ions into cells, leading an increase in intracellular osmolarity. This triggers pyroptosis pathway, resulting cellular contents, inflammatory factors, damage-associated molecular patterns, which ultimately boost responses. Furthermore, inhibit escape through upregulating major histocompatibility complex-I (MHC-I) expression. Collectively, significantly growth metastasis pyroptosis-induced activation MHC-I expression upregulation-remitted research offers novel approach treatment that leverages pyroptosis, demonstrating potential for application

Язык: Английский

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Tandem-controlled lysosomal assembly of nanofibres induces pyroptosis for cancer immunotherapy

Nature Nanotechnology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Язык: Английский

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A Self‐Adaptive Pyroptosis Inducer: Optimizing the Catalytic Microenvironment of Nanozymes by Membrane‐Adhered Microbe Enables Potent Cancer Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 36(14)

Опубликована: Дек. 28, 2023

Pyroptosis has garnered increasing attention in cancer immunotherapy. Moreover, plasma membrane damage by reactive oxygen species (ROS) is considered an effective strategy for promoting pyroptosis. However, the current tactics enhancing rupture pyroptosis are limited inherent drawbacks of ROS and immunosuppressive tumor microenvironment. Herein, a self-adaptive inducer (LPZ) designed integrating Lactobacillus rhamnosus GG (LGG) enzyme-like metal-organic framework to achieve potent LPZ can adhere cell membranes through interaction between pili LGG mucin cells. In particular, adaptive formula gradually enhance ability nanozymes produce creating acidic microenvironment anaerobic respiration. These results verify that could generate high levels both on within cells, leading pyroptotic death strong antitumor immunity. Meanwhile, eventually killed this process halt their respiration prevent potential biosafety concerns. Overall, work provides new inspiration design nanocatalytic drugs

Язык: Английский

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Activated aggregation‐induced emission therapeutics agents for triggering regulated cell death

Aggregate, Год журнала: 2024, Номер 5(3)

Опубликована: Янв. 22, 2024

Abstract The induction of regulated cell death (RCD) through photo/ultrasound sensitization therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors. Aggregation‐induced emission (AIE) generate reactive oxygen species activation, which can synergize with RCD inducers or directly induce RCD, ultimately resulting the tumor cells. presented comprehensive review delves into recent advancements AIE designed trigger inducers, encompassing apoptosis, necroptosis, pyroptosis, immunogenic death, autophagy, ferroptosis, and cuproptosis. Additionally, intricate regulatory mechanisms activatory‐AIE therapeutics influence distinct pathways are examined. A forward‐looking perspective on future developments pertinent challenges within this exciting realm is presented, anticipating continued evolution activatable transformative enhance therapy.

Язык: Английский

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Hypoxia-accelerating pyroptosis nanoinducers for promoting image-guided cancer immunotherapy

Biomaterials, Год журнала: 2024, Номер 309, С. 122610 - 122610

Опубликована: Май 11, 2024

Язык: Английский

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Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy

Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 438 - 452

Опубликована: Май 6, 2024

Язык: Английский

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Disrupting Intracellular Homeostasis by Copper‐Based Nanoinducer with Multiple Enzyme‐Mimicking Activities to Induce Disulfidptosis‐Enhanced Pyroptosis for Tumor Immunotherapy

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Окт. 29, 2024

Given the crucial role of abnormal homeostasis in tumor cells for maintaining their growth, it may be more efficient with less effort to develop anti-tumor strategies that target multiple combined mechanisms by disrupting intracellular homeostasis. Here, a copper-based nanoinducer (CGBH NNs) enzyme-like activities is designed and constructed induce disulfidptosis-enhanced pyroptosis through effective immunotherapy. Within microenvironment (TME), CGBH NNs can disrupt glucose inhibit NADPH production, leading accumulation cystine, which further blocked substrate key enzyme synthesizing glutathione. Subsequently, cascade catalytic reactions involving (glutathione peroxidase-like, oxidase peroxidase-like activities), produce massive reactive oxygen species (ROS) redox homeostasis, resulting pyroptosis. The undergoing immunogenic release various cytosolic contents inflammatory factors, eliciting robust immune responses facilitating cell infiltration, reprogramming immunosuppressive TME. After combination checkpoint blockade therapy, effectively suppress growth prolong survival time tumor-bearing mice. This work presents novel paradigm trigger destroying

Язык: Английский

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A Cu‐Based Single‐Atom Nanozyme Platform with Multi‐Enzyme Simulated Activities for Immunotherapy of Prostate Cancer by Regulating Cholesterol Metabolism and Triggering Pyroptosis

Advanced Functional Materials, Год журнала: 2024, Номер 34(46)

Опубликована: Июнь 10, 2024

Abstract Immunotherapy, one of the most promising antitumor strategies, is used to treat prostate cancer (PCa). However, owing immunosuppressive tumor microenvironment (TME), therapeutic effect immune response greatly weakened. Therefore, there an urgent need explore new methods enhance responses. In this study, a single‐atom nanozyme platform (Cu SA‐DOX@COD) that can trigger pyroptosis developed activate responses via gasdermin E (GSDME)‐dependent pathway. It triggered by catalyzing production reactive oxygen species (ROS) and depleting reduced glutathione through intrinsic multi‐enzyme simulated activities providing source for cholesterol (CHOL) oxidation. Meanwhile, loaded CHOL oxidase not only reduces content cells increase cell membrane permeability inhibit proliferation invasion but also oxidizes increases level H 2 O in pyroptosis. addition, doxorubicin activated caspase‐3 cleave GSDME further augment Consequently, Cu SA‐DOX@COD enhances immunocompetence reshapes TME triggering caused ROS storm, chemotherapy, CHOL, thereby activating systemic immunity PCa.

Язык: Английский

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