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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Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(35)

Опубликована: Июнь 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Язык: Английский

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Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Апрель 6, 2024

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based

Язык: Английский

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A Copper/Ferrous‐Engineering Redox Homeostasis Disruptor for Cuproptosis/Ferroptosis Co‐Activated Nanocatalytic Therapy in Liver Cancer

Advanced Functional Materials, Год журнала: 2024, Номер 34(37)

Опубликована: Апрель 25, 2024

Abstract Cuproptosis and ferroptosis hold great promise for overcoming apoptotic resistance in liver cancer based on their unique metal‐driven cell death modalities. However, insufficient intracellular copper iron concentration, complicated tumor microenvironment (TME), unclear cross‐regulatory mechanisms between cuproptosis ferroptosis, severely restrict the therapeutic performance. Herein, copper‐doped hollow Prussian blue (CHP) nanozymes are rationally designed loading photosensitizer indocyanine green (ICG) O 2 ‐saturated perfluorohexane (PFH), denoted as ‐PFH@CHPI nanoparticles, to induce ferroptosis. In response specific TME, CHP can synergistically catalyze Fenton reactions consume endogenous glutathione, leading accumulation of reactive oxygen species. Upon near‐infrared irradiation, ‐PFH@CHPI‐enabled photothermal effect simultaneously accelerate catalytic trigger release photodynamic therapy promote oxidative stress. Notably, be effectively activated through Cu + ‐mediated dihydrolipoamide S‐acetyltransferase aggregation Fe–S cluster protein loss. Concurrently, tilt redox balance is favorable lipid peroxidation glutathione peroxidase 4 inactivation, resulting an augmented effect. Mechanistically, stress‐boosted jointly disrupt mitochondrial metabolism, which turn exacerbates stress, thus realizing a mutually enhanced This work may provide new guidance utilizing copper/ferrous‐engineering cuproptosis/ferroptosis synergetic therapy.

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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A cuproptosis nanocapsule for cancer radiotherapy

Nature Nanotechnology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 19, 2024

Язык: Английский

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Biomimetic copper-doped polypyrrole nanoparticles induce glutamine metabolism inhibition to enhance breast cancer cuproptosis and immunotherapy

Journal of Controlled Release, Год журнала: 2024, Номер 371, С. 204 - 215

Опубликована: Май 31, 2024

Язык: Английский

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A singular plasmonic-thermoelectric hollow nanostructure inducing apoptosis and cuproptosis for catalytic cancer therapy

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

Опубликована: Авг. 29, 2024

Thermoelectric technology has recently emerged as a distinct therapeutic modality. However, its effectiveness is significantly limited by the restricted temperature gradient within living organisms. In this study, we introduce high-performance plasmonic-thermoelectric catalytic therapy utilizing urchin-like Cu

Язык: Английский

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Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Язык: Английский

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Selective Ions Exchange Reactions Endow Defective Heterovalent Copper‐Based Selenides With Enhanced Dielectric Polarization Response

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Abstract Defective heterovalent selenides provide a spacious arena for creating emergent electromagnetic (EM) phenomena that are unattainable in the conventional constituent counterparts. However, there still synthetic methodological challenges, and in‐depth understanding of EM properties, particularly correlation between tailored polarization sites dielectric response, significantly inadequate. Herein, selective ions exchange strategy driven by concentration‐regulated ( Case 1 ) time‐evoked 2 approaches, is innovatively proposed to design series defective copper‐based selenides. The controllable phase evolution mixed cation/anion responsible heterointerfaces levels ), while Cu + /Cu 2+ electronic configurations controlled cation accounted further manipulating heterointerfaces/defects enriching ). coupling nonstoichiometric 2−x Se‐containing heterointerfaces, unsaturated Se vacancies multi‐valence configurations, rather than themselves alone even at higher level, imparted abundant trigger boosted response Consequently, this designed selenide (ZnSe/CuSe/Cu 2‐x Se) deliveres broad bandwidth 6.89 GHz compare parent ZnSe without outperforming most reported metal until now. This innovative overcame bottlenecks methodology, providing paradigm fabricating sophisticated materials versatile applications beyond absorption.

Язык: Английский

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