Huang, Y;
Gu, B;
Salles-Crawley, II;
Taylor, KA;
Yu, L;
Ren, J;
Liu, X;
Emerson, M;
Longstaff, C;
Hughes, AD;
et al.
Huang, Y; Gu, B; Salles-Crawley, II; Taylor, KA; Yu, L; Ren, J; Liu, X; Emerson, M; Longstaff, C; Hughes, AD; Thom, SA; Xu, XY; Chen, R
(2021)
Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy.
Sci Adv, 7 (23).
ISSN 2375-2548
https://doi.org/10.1126/sciadv.abf9033
SGUL Authors: Salles-Crawley, Isabelle Irene
Abstract
Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.
Item Type: |
Article
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Additional Information: |
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
https://creativecommons.org/licenses/by/4.0/
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Sci Adv |
ISSN: |
2375-2548 |
Dates: |
Date | Event |
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4 June 2021 | Published | 2 June 2021 | Published Online | 14 April 2021 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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URI: |
https://openaccess.sgul.ac.uk/id/eprint/113732 |
Publisher's version: |
https://doi.org/10.1126/sciadv.abf9033 |
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