Self-Reinforced Bimetallic Mito-Jammer for Ca 2+ Overload-Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization
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 bas...
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Published in | Advanced science Vol. 11; no. 15; p. e2306031 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
01.04.2024
|
Subjects | |
Online Access | Get full text |
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Summary: | 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
) into hyaluronic acid (HA) -modified metal-organic frameworks (MOF). After cellular, Mito-Jammer dissociates into CaO
and Cu
in the tumor microenvironment. The exposed CaO
further yields hydrogen peroxide (H
O
) and Ca
in a weakly acidic environment to strengthen the Cu
-based Fenton-like reaction. Furthermore, the combination of chemodynamic therapy and Ca
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. |
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ISSN: | 2198-3844 2198-3844 |
DOI: | 10.1002/advs.202306031 |