Chirality and Nanotechnology Speed Up Light-Based Drug Screening

A team of international collaborators has introduced a drug-screening technique that relies on nanostructure chirality as its fundamental property. (Chirality is a quality that, for a physical object, means it cannot be superimposed on its mirror image; think “left hand/right hand.”) The new technique uses gold nanorods to twist light, and a red glow can indicate the failure of a medication aimed at treating diseases such as Type 2 diabetes and pancreatic cancer.

Chiral nanostructures — in the study, a protein marker for such amyloid diseases called islet amyloid polypeptides — link into twisted, fibrous chains and accumulate in tissue in the shape of corkscrews. These proteins coated the 50-nm-long, 20-nm-wide gold nanorods, forming spring-shaped fibers with three nanorods per turn. Because the chiral shapes of the structures can turn the polarization of light, the structures appeared bright red when researchers viewed them between two oppositely angled light polarizers.

The light-twisting effect enabled the researchers to see the drug screening results with the naked eye as opposed to with instruments. “The periodic helical chains increase the twisting of light by 4600 times, which makes them visible under very difficult biological conditions,” said Nicholas Kotov, co-corresponding author of the paper describing the research. “And the nanorods also speed up the process of forming amyloid chains, which is critical for rapid drug discovery.”

In a device that can reveal whether amyloid proteins are assembling into chains, unpolarized light enters a horizontal polarizer. This only allows waves oscillating in the horizontal direction to get through. Then, if the amyloid proteins have assembled the gold nanorods into chains, red light gets twisted, changing the angle of its polarization. Then, when it passes through the vertical polarizer, the portion of the light oscillating in the vertical direction gets through. This results in a strong red signal that can be seen with the naked eye. Courtesy of Jun Lu, Jilin University and University of Michigan.

Kotov is the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering at the University of Michigan. Additional collaborators are from Jilin University (China) and the Federal University of São Carlos (Brazil).

The nanorods in the system are coated with a surfactant chemical, cetrimonium chloride, allowing the amyloid polypeptides linkage process to occur in one day; typically, amyloid polypeptides take days to link up. The surfactant helps the amyloid proteins that bind to the barrel of the gold rod form a coiled shape, which is necessary to facilitate their bonding to other amyloids. When the amyloids do connect, their gold rods form a helix around the protein structure. Gold, which interacts strongly with red light, ensures that the helices strongly twist the produced red light and deliver a strong indicator of drug performance.

In the device on the left, gold nanorods permit a small amount of light through the two crossed polarizers. This is akin to the signal showing that a drug designed to prevent amyloid plaques from forming is working. However, when the amyloid proteins assemble the gold nanorods into helices, a clear red light is visible through the polarizers, revealing that a drug has failed. Courtesy of Jun Lu, Jilin University and University of Michigan.

The method specifically indicates whether a drug has prevented amyloid chains. It involves two polarizers, between which is a mixture of cells, blood components, drug molecules, and the amyloid proteins that the drugs encounter in the body. The first polarizer allows light to pass only if it oscillates in the vertical direction. The second polarizer allows light to pass only if it oscillates in the horizontal direction.

If the light cannot twist between the polarizers, the light is fully blocked by the apparatus. This occurs when a drug is working successfully — a few nanorods may twist light, but very little light comes through the polarizers.

If the red light-twisting chains do form, a red glow is visible, and the drug is failing.

The view through the polarizer shows where light-twisting structures have formed in a soup of cells and biological materials. Courtesy of Jun Lu, Jilin University and University of Michigan.

The study was funded by the National Natural Science Foundation of China; Jilin University; State Key Laboratory of Supramolecular Structure and Materials; Brazilian funding agencies CAPES, CNPq, and FAPESP; National Science Foundation; and Office of Naval Research.

The study was published in Science (www.doi.org/10.1126/science.abd8576).