The coagulation of blood is necessary to avoid bleeding and is regulated by thrombin and other enzymes, which ensure a rapid and localized response to injury. However, as the world population continues to age, the number of thrombophilic disorders that require therapies with anticoagulants, such as deep venous thrombosis, strokes or heart attacks, increases as well. The most widespread anticoagulants are heparin, warfarin and aspirin, which are dispensed to over 25 million US citizens. Nevertheless, anticoagulants suffer side effects, most usually a high risk of bleeding, which causes them to rank the first cause of death in adverse drug reactions between 1999-2006. This is exacerbated by the fact that anticoagulants are administered in the entire bloodstream, and do not have a specific and effective antidote, so their effect can only be reduced by physiological clearance, and control over blood clotting is inherently one-sided. To overcome these challenges, we have worked towards developing a method to externally control blood clotting by exploiting the optical properties of gold nanoparticles, which represents a great improvement over the current practice of systemically administering anticoagulants and relying on physiological clearance to return the system to normal activity.
Gold nanorods are attractive for externally controlled release of biomolecules by laser irradiation of the nanorods at their surface plasmon resonance, which is tunable by changing the nanorod aspect ratio. Therefore, nanorods with different aspect ratios can be independently excited to release different payloads. This approach can be used to create a biological switch for blood clotting by releasing thrombin binding aptamers (TBA) and their antidotes upon laser irradiations. The TBA and its antidote can be loaded onto nanorods with different aspect ratios. Formation of blood clots is prevented by laser irradiation of the nanorod mixture, which results in the selective release of only the TBA and thus, thrombin inhibition. After, laser irradiation at another wavelength is used to deliver the antidote to specifically reverse the effects of the aptamer and return blood clotting activity to normal (Fig.1). Therefore, a pair of nanorods acts as an on/off switch for blood clotting. This novel approach to treat blood clotting was published in July 2013 in PLoS ONE, and represents an advance for blood clotting therapies and also for numerous other applications that utilize drug release.
Fig. 1: Gold nanorods can be used to control blood clotting. Selective release of an aptamer (red) and then its antidote (blue) by laser excitation of nanorods can switch clotting off and then back on.
Thesis advisor: Dr. Kimberly Hamad-Schifferli