Heterojunction nanozyme achieve highly efficient antibacterial by cuproptosis-like death and ferroptosis-like death
4 affiliations
- 1College and Hospital of Stomatology, Anhui Medical University, Key Lab of Oral Diseases Research of Anhui Province, Hefei, 230032, PR China; School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, PR China
- 2School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, PR China
- 3College and Hospital of Stomatology, Anhui Medical University, Key Lab of Oral Diseases Research of Anhui Province, Hefei, 230032, PR China
- 4Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei, 230041, PR China; School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, PR China; Corresponding author. Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei, 230041, PR China.
Abstract
Metal-ion-mediated lethal pathways offers a highly potent strategy for antibacterial treatments. However, relying on single-pathway mechanisms often fails to overwhelm bacterial antioxidant defenses, reducing antibacterial efficacy. This study designed a heterojunction nanozyme (Cu 2 O/Fe 2 O 3 ) that induces ferroptosis-like death and copper-mediated metabolic toxicity exhibiting cuproptosis-like features, achieving highly effective antibacterial treatment. Computational chemistry analysis indicates that the Cu 2 O/Fe 2 O 3 heterointerface establishes a built-in electric field through spontaneous interfacial electron transfer, thereby enhancing its peroxidase (POD)-like activity. Within the acidic bacterial microenvironment, Cu 2 O/Fe 2 O 3 catalyzes the generation of large amounts of reactive oxygen species (ROS) and releases metal ions, inducing and amplifying ferroptosis-like death, which disrupts the function of ETC enzymes by attacking iron–sulfur clusters. Concurrently, copper ions disrupt the redox balance by depleting bacillithiol (BSH), indirectly increasing bacterial susceptibility and promoting ferroptosis-like death. Furthermore, the accumulation of copper ions triggers severe metabolic impairments that biochemically resemble the cuproptosis cascade, which disrupts key enzymes of the TCA cycle and impairs the synthesis of electron donors (NADH and FADH2), thereby cutting off the supply of substrates to ETC at the upstream stage. Overall, this study demonstrates that triggering bimetallic ion-mediated metabolic disruptions induces an energy crisis in bacteria, providing a reference for multimodal antibacterial strategies.
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BibTeX
@article{wang2026heterojunction,
title = {{Heterojunction nanozyme achieve highly efficient antibacterial by cuproptosis-like death and ferroptosis-like death}},
author = {Wenqi Wang and Ruiyuan Zhu and Hengshuo Gui and Xu Jin and Xiaolong Wei and Xianwen Wang},
journal = {Bioactive Materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.10.020},
url = {https://doi.org/10.1016/j.bioactmat.2026.10.020},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Heterojunction nanozyme achieve highly efficient antibacterial by cuproptosis-like death and ferroptosis-like death
AU - Wenqi Wang
AU - Ruiyuan Zhu
AU - Hengshuo Gui
AU - Xu Jin
AU - Xiaolong Wei
AU - Xianwen Wang
PY - 2026
DA - 2026/10/23
JO - Bioactive Materials
DO - 10.1016/j.bioactmat.2026.10.020
UR - https://doi.org/10.1016/j.bioactmat.2026.10.020
AB - Metal-ion-mediated lethal pathways offers a highly potent strategy for antibacterial treatments. However, relying on single-pathway mechanisms often fails to overwhelm bacterial antioxidant defenses, reducing antibacterial efficacy. This study designed a heterojunction nanozyme (Cu 2 O/Fe 2 O 3 ) that induces ferroptosis-like death and copper-mediated metabolic toxicity exhibiting cuproptosis-like features, achieving highly effective antibacterial treatment. Computational chemistry analysis indicates that the Cu 2 O/Fe 2 O 3 heterointerface establishes a built-in electric field through spontaneous interfacial electron transfer, thereby enhancing its peroxidase (POD)-like activity. Within the acidic bacterial microenvironment, Cu 2 O/Fe 2 O 3 catalyzes the generation of large amounts of reactive oxygen species (ROS) and releases metal ions, inducing and amplifying ferroptosis-like death, which disrupts the function of ETC enzymes by attacking iron–sulfur clusters. Concurrently, copper ions disrupt the redox balance by depleting bacillithiol (BSH), indirectly increasing bacterial susceptibility and promoting ferroptosis-like death. Furthermore, the accumulation of copper ions triggers severe metabolic impairments that biochemically resemble the cuproptosis cascade, which disrupts key enzymes of the TCA cycle and impairs the synthesis of electron donors (NADH and FADH2), thereby cutting off the supply of substrates to ETC at the upstream stage. Overall, this study demonstrates that triggering bimetallic ion-mediated metabolic disruptions induces an energy crisis in bacteria, providing a reference for multimodal antibacterial strategies.
SN - 2452-199X
ER -