Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Год журнала: 2023, Номер 36(8)

Опубликована: Окт. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Язык: Английский

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Cuproptosis: Harnessing Transition Metal for Cancer Therapy

ACS Nano, Год журнала: 2023, Номер 17(20), С. 19581 - 19599

Опубликована: Окт. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Язык: Английский

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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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Photocatalytic Carbon Dots‐Triggered Pyroptosis for Whole Cancer Cell Vaccines

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Авг. 12, 2024

Abstract Manufacturing whole cancer cell vaccines (WCCV) with both biosafety and efficacy is crucial for tumor immunotherapy. Pyroptotic cells, due to their highly immunogenic properties, present a promising avenue the development of WCCV. However, successful WCCV based on pyroptotic cells yet be accomplished. Here, facile strategy that utilized photocatalytic carbon dots (CDs) induce pyroptosis fabricating reported. Photocatalytic CDs are capable generating substantial amounts hydroxyl radicals can effectively decrease cytoplasmic pH values under white light irradiation. This process efficiently triggers through reactive oxygen species (ROS)‐mitochondria‐caspase 3‐gasdermin E pathway proton motive force‐driven mitochondrial ATP synthesis pathway. Moreover, in vitro, these CDs‐induced (PCIP) hyperactivate macrophage (M0–M1) upregulation major histocompatibility complex class II expression. In vivo, PCIP induced specific immune‐preventive effects melanoma breast mouse models anticancer immune memory, demonstrating effective work provides novel insights inducing bridges gap fabrication cells.

Язык: Английский

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Recent advances in the metal/organic hybrid nanomaterials for cancer theranostics

Coordination Chemistry Reviews, Год журнала: 2024, Номер 504, С. 215654 - 215654

Опубликована: Янв. 20, 2024

Язык: Английский

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Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

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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A mitochondria-targeted anticancer copper dithiocarbamate amplifies immunogenic cuproptosis and macrophage polarization

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(8), С. 2006 - 2014

Опубликована: Янв. 1, 2024

A mitochondrial targeting copper dithiocarbamate induces intense immunogenic cuproptosis in cancer cells and macrophage M1 polarization. This emphasizes the potential of inducers immunotherapy.

Язык: Английский

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Multifunctional Au@AgBiS₂ Nanoparticles as High‐Efficiency Radiosensitizers to Induce Pyroptosis for Cancer Radioimmunotherapy

Advanced Science, Год журнала: 2023, Номер 10(30)

Опубликована: Сен. 8, 2023

Radiotherapy (RT), a widely used clinical treatment modality for cancer, uses high-energy irradiation reactive oxygen species (ROS) production and DNA damage. However, its therapeutic effect is primarily limited owing to insufficient damage tumors harmful effects on normal tissues. Herein, core-shell structure of metal-semiconductors (Au@AgBiS2 nanoparticles) that can function as pyroptosis inducers both kill cancer cells directly trigger robust anti-tumor immune against 4T1 triple-negative murine breast metastasis rationally designed. Metal-semiconductor composites enhance the generation considerable ROS simultaneously RT sensitization. Moreover, Au@AgBiS2 , inducer, induces caspase-3 protein activation, gasdermin E cleavage, release damage-associated molecular patterns. In vivo studies in BALB/c mice reveal nanoparticles combined with exhibit remarkable antitumor activity, preventing tumor growth, lung metastasis. Therefore, this an alternative designing highly effective radiosensitizers radioimmunotherapy.

Язык: Английский

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A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

ACS Nano, Год журнала: 2023, Номер 17(20), С. 20445 - 20461

Опубликована: Окт. 6, 2023

Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis an iodine- ferrocene-loaded covalent organic framework (COF) nanozyme, termed TADI-COF-Fc, for enhancement radiotherapeutic efficacy in treatment radioresistant esophageal cancer. The iodine atoms on COF not only exerted a direct effect radiotherapy, increasing its X-ray absorption, but also promoted radiolysis water, increased production reactive oxygen species (ROS). In addition, ferrocene surface decoration disrupted redox homeostasis levels hydroxyl lipid peroxide radicals depleting intracellular antioxidants. Both vitro vivo experiments substantiated excellent response TADI-COF-Fc. This study demonstrates potential COF-based multinanozymes as radiosensitizers suggests possible integration strategy combination oncotherapy.

Язык: Английский

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