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 Biotechnoljournal_title
Nature biotechnologyauthors
Murciano JC,Medinilla S,Eslin D,Atochina E,Cines DB,Muzykantov VRdoi
10.1038/nbt846subject
Has Abstractpub_date
2003-08-01 00:00:00pages
891-6issue
8eissn
1087-0156issn
1546-1696pii
nbt846journal_volume
21pub_type
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