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

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Murciano JC,Medinilla S,Eslin D,Atochina E,Cines DB,Muzykantov VR

doi

10.1038/nbt846

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

891-6

issue

8

eissn

1087-0156

issn

1546-1696

pii

nbt846

journal_volume

21

pub_type

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