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 language | English |
|---|---|
| Pages (from-to) | 891-896 |
| Number of pages | 6 |
| Journal | Nature Biotechnology |
| Volume | 21 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Aug 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Microbiology
Cite this
Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. / Murciano, Juan Carlos; Medinilla, Sandra; Eslin, Donald; Atochina-Vasserman, Elena Nikolaevna; Cines, Douglas B.; Muzykantov, Vladimir R.
In: Nature Biotechnology, Vol. 21, No. 8, 01.08.2003, p. 891-896.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes
AU - Murciano, Juan Carlos
AU - Medinilla, Sandra
AU - Eslin, Donald
AU - Atochina-Vasserman, Elena Nikolaevna
AU - Cines, Douglas B.
AU - Muzykantov, Vladimir R.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nbt846
DO - 10.1038/nbt846
M3 - Article
VL - 21
SP - 891
EP - 896
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
IS - 8
ER -