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.
UR - http://www.scopus.com/inward/record.url?scp=0042855871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042855871&partnerID=8YFLogxK
U2 - 10.1038/nbt846
DO - 10.1038/nbt846
M3 - Article
C2 - 12845330
AN - SCOPUS:0042855871
VL - 21
SP - 891
EP - 896
JO - Bio/Technology
JF - Bio/Technology
SN - 1087-0156
IS - 8
ER -