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Fibrinogen-mimicking, multi-arm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy
File(s)
Author(s)
Huang, Yu
Gu, Boram
Salles, Isabelle I
Taylor, Kirk A
Yu, Li
Type
Journal Article
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, multi-arm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This novel 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 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.
Date Issued
2021-06-02
Date Acceptance
2021-04-14
Citation
Science Advances, 2021, 7 (23)
URI
DOI
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Journal / Book Title
Science Advances
Volume
7
Issue
23
Copyright Statement
© 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.
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Engineering & Physical Science Research Council (EPSRC)
Grant Number
RDB02
EP/R013764/1
Publication Status
Published
Article Number
ARTN eabf9033