A Golden On-Off Switch

Using gold nanoparticles, MIT researchers have devised a new way to turn blood clotting on and off. The particles, which are controlled by infrared laser light, could promote wound healing or help doctors regulate blood clotting in patients undergoing surgery.

Blood clotting is produced by a long cascade of protein interactions, culminating in the formation of fibrin, a fibrous protein that seals wounds. Heparin and other blood thinners interfere with this process by targeting several of the reactions that occur during the blood-clotting cascade. But there’s no way to counteract the effects of blood thinners. “It’s like you have a light bulb, and you can turn it on with the switch just fine, but you can’t turn it off. You have to wait for it to burn out,” says Kimberly Hamad-Schifferli ’94, a technical staff member at MIT Lincoln Laboratory. She says a better solution would be an agent that targets only the last step—the conversion of fibrinogen to fibrin, a reaction mediated by an enzyme called thrombin.

Several years ago, scientists discovered that DNA with a specific sequence inhibits thrombin by blocking the site where it would typically bind to fibrinogen. The complementary DNA sequence can shut off the inhibition—and turn blood clotting back on—by binding to the original thrombin-inhibiting DNA strand and preventing it from attaching to thrombin.

Hamad-Schifferli and her colleagues had previously shown that gold nanorods bound to drugs or other compounds can be designed to release them when exposed to infrared light. The size of the nanorod determines the wavelength of light that will activate this process. To manipulate the blood-­clotting cascade, the researchers loaded a smaller gold nanorod (35 nanometers long) with the DNA thrombin inhibitor; a larger particle (60 nanometers long) was loaded with the complementary DNA strand.

Under the correct wavelength of infrared light, the electrons within the gold become very excited and generate so much heat that they melt slightly, taking on a more spherical shape and releasing their DNA payload.

The researchers have successfully tested the particles in human blood samples and are now engineering them so they can travel to injury sites where they would be needed.