Researchers successfully used motorized molecules driven by light to drill holes in the membranes of individual cells. This shows promise to bring therapeutic agents into cells or directly inducing cells to die. Researchers from the laboratories of James Tour at Rice, Robert Pal at Durham, and Gufeng Wang at North Carolina State demonstrated in lab tests how rotors in single-molecule nanomachines can be activated by ultraviolet light to spin at 2 to 3 million rotations per second and open membranes in cells in this week's Nature.
"We thought it might be possible to attach these nanomachines to the cell membrane and then turn them on to see what happened," Tour said. The motors, only about a nanometer wide, can be designed to target and then either tunnel through a cell's lipid bilayer membrane to deliver drugs or other payloads or disrupt the 8-10 nanometer-wide membrane, thereby killing the cell. They can also be functionalized for solubility and for fluorescent tracking, he said.
The Rice lab created 10 variants, including motor-bearing molecules in several sizes and peptide-carrying nanomachines designed to target specific cells for death, as well as control molecules identical to the other nanomachines but without motors. Then, the Wang Lab tested the motorized molecule's ability to open a synthetic lipid bilayer vesicle, allowing a dyed solution to get inside. They then trapped dye-carrying molecular motors inside a vesicle, activated them with ultraviolet light and watched as the fluorescent dye faded, which suggested the motor had gone through the vesicle wall.
Since they saw that the motor could get through the synthetic lipid bilayer vesicle, Pal's labroatory then tested to see if the motors could work in live human prostate cancer cells. The experiments showed that without an ultraviolet trigger, motors could locate specific cells of interest but stayed on the targeted cells' surface and were unable to drill into the cells. When triggered, however, the motors rapidly drilled through the membranes.
"Test motors designed to target prostate cancer cells broke through their membranes from outside and killed them within one to three minutes of activation," Pal said. "It is highly unlikely that a cell could develop a resistance to molecular mechanical action," Tour noted.
The researchers are now working on experiments in microorganisms and small fish. They hope to then move onto rodents to test the efficacy of nanomachines for a wide range of medicinal therapies.
Image: Motorized molecules that target diseased cells may deliver drugs to or kill the cells by drilling into the cell membranes. Scientists at Rice, Durham (U.K.) and North Carolina State universities have demonstrated them on cancer and other cells. Image courtesy of Loïc Samuel/Rice University.