Cabrera, D ORCID: https://orcid.org/0000-0001-7912-9939, Eizadi Sharifabad, M, Ranjbar, J, Telling, ND ORCID: https://orcid.org/0000-0002-2683-5546 and Harper, AGS ORCID: https://orcid.org/0000-0003-2413-4823 (2022) Clot-Targeted Magnetic Hyperthermia Permeabilizes Blood Clots to Make Them More Susceptible to Thrombolysis. Journal of Thrombosis and Haemostasis.

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J of Thrombosis Haemost - 2022 - Cabrera - Clot‐targeted magnetic hyperthermia permeabilizes blood clots to make them more.pdf - Accepted Version
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Abstract

BACKGROUND: Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways.However, it is only effective within 4.5 hours of symptom onset due to clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles are used to treat cancer by using local heat generation to trigger apoptosis of cancer cells. OBJECTIVES: To develop clot-targeting magnetic nanoparticles to deliver MH to the surface of human blood clots, and to assess whether this can improve the efficacy of thrombolysis of contracted blood clots. METHODS: Clot-targeting magnetic nanoparticles were developed by functionalizing iron oxide nanoparticles with an antibody recognizing activated integrin αIIbβ3 (PAC-1). The magnetic properties of the PAC-1-tagged magnetic nanoparticles were characterized and optimized to deliver clot-targeted MH. RESULTS: Clot-targeted MH increases the efficacy of tPA-mediated thrombolysis in contracted human blood clots, leading to a reduction in clot weight. MH increases the permeability of the clots to tPA, facilitating their breakdown. Scanning electron microscopy reveals that this effect is elicited through enhanced fibrin breakdown and triggering the disruption of red blood cells on the surface of the clot. Importantly, endothelial cells viability in a 3D blood vessel model is unaffected by exposure to MH. CONCLUSIONS: This study demonstrates that clot-targeted MH can enhance the thrombolysis of contracted human blood clots and can be safely applied to enhance the timeframe in which thrombolysis is effective.

Item Type: Article
Additional Information: The final version of this accepted manuscript will be available directly from the publisher at https://onlinelibrary.wiley.com/journal/15387836. Refer to any relevant terms and conditions
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 11 Aug 2022 11:32
Last Modified: 31 Aug 2022 08:41
URI: https://eprints.keele.ac.uk/id/eprint/11247

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