When activated by ultraviolet light, a molecular motor can whirl its way into cells, report chemists. Such molecular drills could create openings for therapeutics to slip through or punch enough holes to destroy a cancer cell’s integrity. “We show that a new generation of therapeutics is coming wherein these machines can open cells—either permitting drugs to enter them or causing the cells to rapidly die,” says James M. Tour, a chemist at Rice University who came up with the idea.
Tour’s research has long focused on creating molecular machines. His lab created the first nanocar. When he explains his research, people often ask him if molecular machines could one day be used to treat disease. Such questions only intensified when molecular machine inventors won the Nobel Prize in Chemistry last year.
Because molecular machines are so much smaller than biological structures, such as cells, Tour didn’t think it was likely that they’d be practical tools for medicine. But then, he says, it occurred to him that surrounding a cell with spinning molecular motors might have interesting results. So he teamed up with Durham University’s Robert Pal, North Carolina State University’s Gufeng Wang, and Rice’s Jacob T. Robinson to explore this idea.
The chemists created several motor molecules based on a design from Nobel Laureate Ben Feringa’s lab at the University of Groningen (Nature 2017, DOI: 10.1038/nature23657). UV light isomerizes a double bond in this motor, spinning a rotor group.
One of these motors had peptide arms that associate with specific proteins on the surface of certain cells. In tests on human prostate cancer cells, the team found that these motors could latch onto the cells and, upon exposure to UV light, destroy them in under three minutes.
“You can just drill holes in cells, something that they’d never be able to build a resistance to,” Tour says. “But it only happens where you shine the light.” That means if the machines latched onto healthy cells elsewhere in the body, the drills would stay inactive and leave the cells alone.
“The observation that motors with appended peptide moieties can selectivity target specific cell surface sites holds considerable promise for future biological applications,” Feringa comments. The next challenge the researchers face, he says, will be to get the same nanomechanical action via visible or near-infrared irradiation, which penetrate more deeply into tissue, so that the motor molecules can be widely used in animals and people.
To that end, Tour says the group is already working on developing motors that spin in response to visible light as well as two-photon infrared radiation.