Therapeutic approaches to life-threatening cardiovascular thrombosis syndromes include the administration of fibrin dissolving (fibrinolytic) drugs, such as recombinant tissue plasminogen activator (rtPA). Unfortunately rtPA  is ineffective in up to 1/3 of thrombotic syndromes, and in addition, carries a significant risk of life-threatening bleeding, including  intracerebral hemorrhage.  In order to circumvent these current limitations, we have conjugated rTPA to a magnetofluorescent nanoscaffold targeted to activated factor XIII (FXIIIa), a transglutaminase expressed preferentially by acutely formed thrombi.  When assayed in vitro the resulting conjugate readily bound to plasma clots as demonstrated by fluorescence imaging. The nanoscaffold also displayed an amidolytic efficiency comparable to unconjugated rtPA  and retained its fibrinolytic activity as determined in turbidimetric and fibrin plate lysis assays.   In vivo, the agent was equally as effective as unconjugated rTPA in lysing acute pulmonary emboli.  Further investigation into the safety/bleeding profile of the nanoagent is currently underway.

Thrombus-targeted theranostic nanoagents for fibrinolysis

240th National Meeting (2010)

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