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Massachusetts Institute of Technology - From Gold nanoparticles, a new way to control blood clotting

Innovative engineers design nanoparticles that can turn the blood-clotting cascade "on or off"

DCN Corp® - A colorized electron micrograph of red blood cells with gold (Au) nano-rods (yellow dots) on their surfaces.  The blue represents a fixing polymer.  Credit - Helena de Puig - MIT, USAExploiting the unique properties of Gold nanoparticles (AuNP) has become an increasing R&D/commercialisation craze.  To that effect - MIT researchers have recently devised a new way to turn blood-clotting "on or off".  The nanoparticles, which can be finitely tuned by infrared laser light (IR) - could help doctors control blood-clotting in patients undergoing surgery or promote monitoring of real-time wound healing.

At present - the only reputable procedure for doctors to manage blood-clotting is by controlled administration of blood thinners, such as heparin (sulfated glycosaminoglycan).  Heparin is known to reduce blood-clotting, but unfortunately there is no way to counter-act the side-effects of heparin and other commonly employed blood thinners.

As stated by Kimberly Hamad-Schifferli, a technical staff member at MIT Lincoln Laboratory and senior author of a journal describing how new nanoparticles can turn blood-clotting off and then restore it when necessary - "It's like you have a light bulb, and you can turn it on with the switch just fine, but you cannot turn it off.  You have to wait for it to burn-out,"

Unfortunately, blood-clotting typically occurs, due to long build-up 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 build-up.  However, a better solution, as Hamad-Schifferli explains, is by an agent which targets only the last step - in other words the conversion of fibrinogen to fibrin, a reaction mediated by an enzyme called thrombin.

A few years ago - scientists discovered that DNA with a specific sequence inhibits thrombin by blocking the site where it would typically bind fibrinogen.  The complementary DNA sequence can shut-off the inhibition by binding to the original DNA strand and preventing it from attaching to thrombin.

Interestingly previously Hamad-Schifferli (and her colleagues) had demonstrated that Gold (Au) nano-rods can be created to release drugs or other compounds when activated with IR light.  Essentially the size of the nano-rod determines the wavelength of light that will activate it, so effectively two rods of different lengths can carry different payloads and be controlled separately.

To manipulate the blood-clotting build-up - Hamad-Schifferli decided to load a smaller Au nano-rod (ca 35 nm long) with the DNA thrombin inhibitor and a larger particle (ca 60 nm long) with the complementary DNA strand.  At first, the researchers tired to get the DNA to chemically bond to the AuNPs, but they found they could not load enough DNA onto each particle to make the process worthwhile.

Alternatively, Hamad-Schifferli - states "We realised we could use a bad side-effect of nanoparticle biology to our advantage." - which is that the particles have a tendency to attract a 'halo' of proteins that bind to Au, making them sticky.  Hamad-Schifferli - continues to state - "If you do that, you get way more drug on the nano-rod than you normally would if you had to chemically link them together,"  Thus, by soaking the nano-rods in a solution of human serum protein and the DNA molecules, the researchers were able to attach six times more DNA than through chemical bonding.  Thereafter when the Au nano-rods are exposed to the correct wavelength of IR light, the electrons within the Au become very excited and generate enough heat, so that they melt slightly and take on a more spherical shape and releasing their DNA payload.

The MIT researchers tested their innovative nanoparticles against blood donated to hospitals, and found that the nanoparticles successfully turned blood-clotting "on and off" in all of the samples tested.  As stated by Luke Lee, a professor of bio-engineering at the University of California at Berkeley who was not part of the MIT research team - "It's really a fascinating idea that you can control blood-clotting not just one way, but by having two different optical antennae to create two-way control," - "It's an innovative and creative way to interface with biological systems."

In summary, for the nanoparticles to be of practical use with patients, then it would have to be targeted to the site of injury via a procedure known as patch theranostics, which the researchers are now working on.  Once the nanoparticles have reached the site, they would need to be within a few millimeters of the skin surface for the IR light shone on the skin to reach them.   In addition, the researchers are also working on modifying the system, so that the nanoparticles can be activated employing a continuous wave laser, which is smaller and less powerful than the pulsed femtosecond laser they are currently employing.  Original article available here

As with similar kind of nano-plasmonic articles - DCN Corp finds the above research extremely interesting, and the company is wondering if it can provide an innovative patch theranostic solution, whereby a colour change indicates the IR light "on or off" effect for blood-clotting.  If so, and you and/or your colleagues are interested in making such a theranostic concept reality - please ensure to contact the company as soon as practicably possible.