Platelets As Contractile Nanomachines For Targeted Drug Delivery In Hemostasis And Thrombosis

PI’s: Wilbur Lam

Hemorrhage remains a major cause of trauma-related fatalities. The few clinically available treatments to abate hemorrhage can lead to uncontrolled clotting and subsequent thrombosis and are ineffective for non-compressible hemorrhage. A clear need exists for targeted delivery systems of hemostatic agents that avoid the drawbacks of current systems and can be employed for non-compressible injuries. We hypothesize that targeted drug delivery to sites of vascular injury can be achieved by leveraging processes that naturally occur during hemostasis. Specifically, incorporating fibrinogen (the monomeric form of fibrin and the major component of blood clots) on the nanocarrier delivery vehicle exterior enables targeting of clotting sites by polymerizing the vehicle into the forming fibrin matrix as well as platelet adhesion. Upon activation, platelets will then contract, rupturing and releasing the loaded therapeutic from the nanocarriers. Therefore, this novel paradigm of platelet/nanocarrier hybrids leverages the chemomechanical action of activated platelets as both the sensor and actuator, and ensures that drug release occurs only at sites requiring hemostatic acceleration.

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