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

被引：166

作者：

Murciano, JC

Medinilla, S

Eslin, D

Atochina, E

Cines, DB

Muzykantov, VR

机构：

[1] Univ Penn, Inst Environm Med, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Div Pediat Hematol, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

来源：

NATURE BIOTECHNOLOGY | 2003年 / 21卷 / 08期

关键词：

D O I：

10.1038/nbt846

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：891 / 896

页数：6

共 50 条

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