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Updated: Aug 16, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
High-Density Co-Based Single-Atom Nanozymes Alleviate Myocardial Ischemia-Reperfusion Injury by Disrupting the Cycle
Bin Zhang1,2, Rui Niu1,3, Shuai Zhang4
1Key Laboratory of Rare Earths, Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, P. R. China.
Abstract:
The vicious cycle of "oxidative stress-ferroptosis-inflammatory response" is a key cause of the progression of myocardial ischemia-reperfusion injury (MIRI), but single antioxidant or anti-inflammatory therapies have not yielded satisfactory therapeutic effects. In this study, we developed a multi-functional nanoregulator (HCoMB) based on high-density Co single-atom nanozyme (HCoN4) for efficient inhibition of MIRI pathological progression, potentially through disruption of the cycle of "oxidative stress-ferroptosis-inflammatory response". HCoN4 with 11.05 wt% Co loading exhibited boosted glutathione peroxidase (GPx)-like activity, superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities due to the increased metal loading, which not only raised the number of catalytic active centers but also effectively improved the intrinsic activity of individual sites via electron transfer between densely distributed active sites. It can efficiently and stably scavenge ROS, upregulate the expression of glutathione peroxidase 4 (GPx4), and block the core pathway of ferroptosis. In addition, the combination with ML355 could specifically block the p53-mediated ferroptosis process by inhibiting ALOX12 activity. Mechanistically, the synergistic effect can significantly alleviate lipid peroxidation and oxidative stress injury in cardiomyocytes, and ultimately break the vicious cascade cycle of oxidative stress, ferroptosis and inflammatory response, and realize effective protection against MIRI.
Insights
A novel nanoregulator (HCoMB) effectively targets the "oxidative stress-ferroptosis-inflammatory response" cycle. This approach shows promise in treating myocardial ischemia-reperfusion injury (MIRI) by protecting heart cells.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Nanomedicine
Background:
- Myocardial ischemia-reperfusion injury (MIRI) progression is driven by a detrimental cycle of oxidative stress, ferroptosis, and inflammation.
- Existing single-target therapies (antioxidant or anti-inflammatory) offer limited efficacy against MIRI.
Purpose of the Study:
- To develop a multi-functional nanoregulator (HCoMB) for inhibiting MIRI progression.
- To investigate the disruption of the "oxidative stress-ferroptosis-inflammatory response" cycle by HCoMB.
Main Methods:
- Fabrication of a high-density cobalt single-atom nanozyme (HCoN4) with high cobalt loading (11.05 wt%).
- Evaluation of HCoN4's enhanced catalytic activities (glutathione peroxidase-like, superoxide dismutase-like, catalase-like).
- Assessment of HCoMB's synergistic effects with ML355 in blocking ferroptosis pathways and protecting cardiomyocytes.
Main Results:
- HCoN4 demonstrated significantly boosted GPx, SOD, and CAT-like activities, enhancing ROS scavenging and ferroptosis inhibition.
- The nanoregulator upregulated glutathione peroxidase 4 (GPx4) expression, blocking ferroptosis.
- Synergistic treatment with ML355 specifically inhibited p53-mediated ferroptosis, alleviating lipid peroxidation and oxidative stress in cardiomyocytes.
Conclusions:
- The developed multi-functional nanoregulator (HCoMB) effectively breaks the vicious cycle of oxidative stress, ferroptosis, and inflammation.
- HCoMB offers a promising therapeutic strategy for mitigating myocardial ischemia-reperfusion injury (MIRI).
