Abstract
Antiplatelet drugs have represented a milestone in treating patients at high risk of thrombosis. However, their clinical use remains limited by bleeding-associated risk and limited efficacy. Excessive reactive oxygen species (ROS) produced by damaged vascular endothelial cells have been shown to stimulate thrombosis. Here we propose that a ROS-chemotactic nanoscavenger (MDCP), formed by crosslinking melanin and catalase, prevents acute thrombosis by protecting vascular endothelial cells from oxidative stress. We demonstrate that treatment with MDCP inhibits ROS-induced apoptosis of endothelial cells, thereby maintaining endothelial integrity and preventing collagen exposure, which consequently prevents platelet activation and thrombosis. By avoiding direct interference with platelet function, this modulation of vascular redox homeostasis via MDCP provides a promising alternative antithrombotic strategy that addresses the bleeding risk of current clinical antithrombotic drugs.
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Data availability
The transcriptomic sequencing data from occlusive coronary thrombi of patients with ST-elevation myocardial infarction and the peripheral blood of healthy donors were retrieved from the GEO under accession number GSE19339. Transcriptome data comparing rat abdominal aortas treated with ferric chloride versus saline control are available in the GEO database under accession number GSE307563. All other data supporting the findings are available within the article and its Supplementary Information, or from the corresponding authors upon request. Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China 82130060 (G.-J.T.), 61821002 (G.-J.T.), 32030060 (X.-J.L.) and 82302364 (Y.Z.), the National Key Research and Development Programme of China 2018YFA0704100 (G.-J.T.) and 2021YFA1201000 (X.-J.L.), and the National Natural Science Foundation of China International Collaboration Key Project 51861135103 (X.-J.L.). We also acknowledge support from the Chinese Academy of Sciences (CAS-NSTDA) International Partnership Programme 121D11KYSB20210003 (X.-J.L.), the China Postdoctoral Science Foundation 2023M730589 (Y.Z.), the Chongqing Municipal High-Level Medical Talents Programme for Young and Middle-Aged Professionals YXGD202401-58 (Y.Z.), the Programme for Youth Innovation in Future Medicine at Chongqing Medical University W0170 (Y.Z.), the Kuanren Talents Programme kryc-gg-2213 (Y.Z.), and the Kuanren Talents Enhancement Programme and the Doctoral Supervisor Cultivation Programme of the Second Affiliated Hospital of Chongqing Medical University (Y.Z.). We thank F. Jia for his assistance with the fabrication of the microfluidic devices and Shanghai OE Biotech Co., Ltd., for quantitative metabolomics analysis. The funding sources had no role in the writing of the report or in the decision to submit the paper for publication.
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Conceptualization: G.-J.T., Y.Z., Q.N. and X.-J.L. Methodology: Y.Z., Q.N., L.H., G.Q., F.Z., Y.L., H.J. and Z.T. Investigation: Y.Z., Q.N., L.H., G.Q., Z.W. and Y.L. Visualization: Y.Z., H.W., Y.L., H.J. and Z.T. Funding acquisition: G.-J.T., X.-J.L. and Y.Z. Supervision: G.-J.T., H.Z. and X.-J.L. Original draft writing: Q.N., Y.Z. and G.Q. Review and editing: Q.N., G.Q., L.J., G.-J.T., N.G. and X.-J.L.
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Extended data
Extended Data Fig. 1 Results of omics analyses and the efficiency of catalase in protecting endothelial cells.
a, Volcano plot illustrating the differential gene expression in occlusive coronary thrombi from patients with ST-elevation myocardial infarction compared with peripheral blood from healthy donors, n = 4. b,c, Volcano plot illustrates differential protein expression in abdominal aorta of rats modelled with saline compared with that of rats modelled with FeCl3 (b), n = 3. These differentially expressed proteins were subsequently enriched in pathways using KEGG database (c). d,e, Heat map illustrates the differential metabolite profiles in the abdominal aorta of rats modelled with saline compared with that of rats modelled with FeCl3 (d), n = 3. These differential metabolites were enriched in the top 20 pathways in KEGG database (e). The colour bar in d represents Z-scores of normalized expression values. f,g, HUVECs were treated with PBS or CAT for 1 hour followed by treatment with XOD for 12 h to assess the efficiency of catalase in preventing XOD-induced apoptosis of endothelial cells. f, Representative CLSM images of endothelial cells stained with Calcein AM/PI, with live cells appearing green (Calcein AM), and dead cells appearing red (propidium iodide, PI). Scale bar, 200 μm. Experiments were replicated three times. g, Representative flow cytometry plots and quantification of the proportion of viable endothelial cells among total cells. Data are presented as mean ± s.d., n = 3 biologically independent samples. Statistical analysis was performed using a two-tailed unpaired Student’s t-test (a,b, and g). Pathway enrichment analysis was performed using the hypergeometric test. Significantly enriched pathways were identified based on a false discovery rate (FDR) < 0.05 (c,e). ns, not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
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Zhong, Y., Ni, Q., Huang, L. et al. Prevention of acute thrombosis with vascular endothelium antioxidative nanoscavenger. Nat. Nanotechnol. 20, 1871–1883 (2025). https://doi.org/10.1038/s41565-025-02046-4
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DOI: https://doi.org/10.1038/s41565-025-02046-4
