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Self-Reinforced Bimetallic Mito-Jammer for Ca 2+ Overload-Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization.
- Source :
-
Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Apr; Vol. 11 (15), pp. e2306031. Date of Electronic Publication: 2024 Feb 11. - Publication Year :
- 2024
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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 and damage-repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self-reinforced bimetallic Mito-Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO <subscript>2</subscript> ) into hyaluronic acid (HA) -modified metal-organic frameworks (MOF). After cellular, Mito-Jammer dissociates into CaO <subscript>2</subscript> and Cu <superscript>2+</superscript> in the tumor microenvironment. The exposed CaO <subscript>2</subscript> further yields hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ) and Ca <superscript>2+</superscript> in a weakly acidic environment to strengthen the Cu <superscript>2+</superscript> -based Fenton-like reaction. Furthermore, the combination of chemodynamic therapy and Ca <superscript>2+</superscript> overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu-ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer.<br /> (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 2198-3844
- Volume :
- 11
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 38342617
- Full Text :
- https://doi.org/10.1002/advs.202306031