Self‐Reinforced Bimetallic Mito‐Jammer for Ca²⁺ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization

Advanced Science, Год журнала: 2024, Номер 11(15)

Опубликована: Фев. 11, 2024

Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature damage‐repair capabilities malignant tumors strongly limit efficacy treatments based on a single treatment mode. To address this challenge, self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) calcium peroxide (CaO 2 ) into hyaluronic (HA) ‐modified metal‐organic frameworks (MOF). After cellular, dissociates CaO Cu 2+ tumor microenvironment. The exposed further yields hydrogen (H O Ca weakly acidic environment to strengthen ‐based Fenton‐like reaction. Furthermore, combination chemodynamic therapy overload exacerbates ROS storms mitochondrial damage, resulting downregulation intracellular adenosine triphosphate (ATP) levels blocking Cu‐ATPase sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic death suppresses metastasis simultaneously. study presents multivariate model for revolutionizing mitochondria relying continuous retention ions boost cuproptosis/immunotherapy cancer.

Язык: Английский

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Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis

ACS Nano, Год журнала: 2024, Номер 18(12), С. 9031 - 9042

Опубликована: Март 12, 2024

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting acid-degradable copper hydride (CuH) nanoparticles was developed via microfluidic synthesis. After coating tumor-targeting hyaluronic acid (HA), denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. can induce apoptosis relying on Fenton-like reactions lead to causing mitochondrial protein aggregation. Besides, existence H2 enhance both cell death types dysfunction intracellular redox homeostatic disorders. In vivo experimental results further exhibit desirable potential HCP for killing inhibiting lung metastases, which will broaden horizons designing materials triggering better efficacy.

Язык: Английский

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Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Current Medical Science, Год журнала: 2024, Номер 44(1), С. 28 - 50

Опубликована: Фев. 1, 2024

Abstract Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, body maintains copper homeostasis. deficiency or excess can adversely affect cellular function. Therefore, homeostasis stringently regulated. Recent studies suggest that trigger specific form of cell death, namely, cuproptosis, which triggered by excessive levels intracellular copper. Cuproptosis induces aggregation mitochondrial lipoylated proteins, loss iron-sulfur cluster proteins. In neurodegenerative diseases, pathogenesis progression neurological disorders are linked to This review summarizes advances cuproptosis nervous system diseases. offers research perspectives provide new insights into targeted treatment diseases based on cuproptosis.

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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