Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes

Juan Carlos Murciano, Sandra Medinilla, Donald Eslin, Elena Nikolaevna Atochina-Vasserman, Douglas B. Cines, Vladimir R. Muzykantov

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123 Citations (Scopus)

Abstract

A fibrinolytic agent consisting of a tissue-type plasminogen activator (tPA) coupled to the surface of red blood cells (RBCs) can dissolve nascent clots from within the clot, in a Trojan horse-like strategy, while having minimal effects on preexisting hemostatic clots or extravascular tissue. After intravenous injection, the fibrinolytic activity of RBC-tPA persisted in the bloodstream at least tenfold longer than did that of free tPA. In a model of venous thrombosis induced by intravenously injected fibrin microemboli aggregating in pulmonary vasculature, soluble tPA lysed pulmonary clots lodged before but not after tPA injection, whereas the converse was true for RBC-tPA. Free tPA failed to lyse occlusive carotid thrombosis whether injected before or after vascular trauma, whereas RBC-tPA circulating before, but not injected after, thrombus formation restored blood flow. This RBC-based drug delivery strategy alters the fibrinolytic profile of tPA, permitting prophylactic fibrinolysis.

Original languageEnglish
Pages (from-to)891-896
Number of pages6
JournalNature Biotechnology
Volume21
Issue number8
DOIs
Publication statusPublished - 1 Aug 2003
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology

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    Murciano, J. C., Medinilla, S., Eslin, D., Atochina-Vasserman, E. N., Cines, D. B., & Muzykantov, V. R. (2003). Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nature Biotechnology, 21(8), 891-896. https://doi.org/10.1038/nbt846