Rice nanomachines constructed to deliver drugs, destroy diseased cells
Motorized molecules driven by light have been used to drill holes in the membranes of individual cells and show promise for either bringing therapeutic agents into the cells or directly inducing the cells to die.
Researchers at Rice, Durham (U.K.) and North Carolina State universities 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.
The researchers used motors based on work by Nobel laureate Bernard Feringa, who won the prize for chemistry in 2016. The motor itself is a paddle-like chain of atoms that can be prompted to move in a single direction when supplied with energy. Properly mounted as part of the cell-targeting molecule, the motor can be made to spin when activated by a light source.
The work detailed this week in Nature was led by chemists James Tour of Rice, Robert Pal of Durham and Gufeng Wang of North Carolina State. Their labs collaborated to create several motorized molecules that can home in on specific cells, and they viewed what happens when they activate the motors with light.
The Tour lab previously demonstrated molecular motors whose diffusion in a solution was enhanced, if not specifically directed, when activated by ultraviolet light. The rotors needed to spin between 2 and 3 megahertz – 2 to 3 million times per second – to show they could overcome obstacles presented by adjacent molecules and outpace natural Brownian motion.
“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.
“These nanomachines are so small that we could park 50,000 of them across the diameter of a human hair, yet they have the targeting and actuating components combined in that diminutive package to make molecular machines a reality for treating disease,” Tour 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.
The Wang lab first successfully tested the motorized molecule’s ability to open a synthetic lipid bilayer vesicle, allowing dyed solution to get inside. Next, they 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 punched through the vesicle wall.
The researchers found it takes at least a minute for a motor to tunnel through a membrane. “It is highly unlikely that a cell could develop a resistance to molecular mechanical action,” Tour said.
Pal expects nanomachines will help target cancers like breast tumors and melanomas that resist existing chemotherapy. “Once developed, this approach could provide a potential step change in noninvasive cancer treatment and greatly improve survival rates and patient welfare globally,” he said.
The Pal lab at Durham tested motors on live cells, including human prostate cancer cells. 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. Videos of the cells showed increased blebbing – bubbling of the membrane – within minutes after activation.
Smaller molecular motors were harder to track but proved better at getting into cells quickly upon ultraviolet activation, disrupting their membranes and killing them. Motorless control molecules were unable to kill cells upon ultraviolet exposure, which eliminated thermal absorption of ultraviolet light as the cause of disruption, according to the researchers.
They expect the rotors may eventually be activated by two-photonabsorption, near-infrared light or radio frequencies, which would make the technique more viable for in-vivo treatment; this would pave the way toward the establishment of novel, easy and cost-effective photodynamic therapy.
“The researchers are already proceeding with experiments in microorganisms and small fish to explore the efficacy in-vivo,” Tour said. “The hope is to move this swiftly to rodents to test the efficacy of nanomachines for a wide range of medicinal therapies.”
Learn more: Motorized molecules drill through cells
The Latest on: Motorized molecules
[google_news title=”” keyword=”motorized molecules” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]- First steps toward a whole-body map of molecular responses to exerciseon May 5, 2024 at 5:50 am
Research definitively confirms that muscle-moving, calorie-burning activity slows the advance of disease, improves cognitive function, boosts the immune system, and reduces rates of mortality from all ...
- Terrifying moment motorized paraglider traveling at 50mph flips over and smashes into the Texas desert - but miraculously SURVIVESon April 27, 2024 at 2:46 pm
A YouTuber is lucky to be alive after crashing his paramotor when it flipped over and plummeted into the desert at 48mph. Anthony Vella, 33, was testing a BGD Luna 3 in the Enchanted Rock State ...
- Roche's pipeline rethink hits 20% of new molecules as cancer candidates join discard pileon April 23, 2024 at 9:27 pm
The culls are part of a broader refocusing that has removed 20% of new molecules from the pipeline in recent quarters. Hanmi, which retained the rights to the asset in South Korea, published data ...
- Buried in the Cat's Paw Nebula lies one of the largest space molecules ever seenon April 23, 2024 at 5:00 pm
Discovering molecule 2-methoxyethanol was remarkable. It contains 13 atoms, which may not sound like a lot, but only six molecules have been discovered in space with an atom count beyond this.
- Rotational Spectroscopy of Diatomic Moleculeson March 9, 2024 at 7:01 am
Zhao, L. B. Stancil, P. C. Gu, J. P. Liebermann, H.‐P. Li, Y. Funke, P. Buenker, R. J. Zygelman, B. Kimura, M. and Dalgarno, A. 2004. Radiative Charge Transfer in ...
- 11 Mistakes You Need To Avoid When Grinding Your Own Meaton December 20, 2023 at 11:37 am
Like any other motorized equipment, the cold environment reduces heat ... Additionally, marinating the meat before grinding can be helpful as the acidic molecules present in vegetables, vinegar, or ...
- Cellular and Molecular Imaging Coreon October 18, 2023 at 1:36 pm
The THUNDER Imager 3D Tissue is a motorized upright microscope and is outfitted with ... including dye-labeled samples), small molecules in organic solvents, kinetics in a drop, and more. It has an ...
- Movement of molecules across the cell membraneon April 30, 2023 at 9:57 pm
This takes place when molecules diffuse across the cell membrane by travelling through specific transport proteins. It occurs down a concentration gradient - molecules move from an area of high to ...
- Heat- Energy on the Moveon December 7, 2022 at 11:42 pm
Heating a substance makes its atoms and molecules move faster. This happens whether the substance is a solid, a liquid, or a gas. It’s not easy to see it happen in a solid but let’s try it for a ...
- SHERLOC And The Search For Life On Marson January 26, 2022 at 11:22 pm
Discovering organic molecules on Mars is far from proof that ... Both cameras have their motorized lens covers in place. For reference, both cameras are about 9 cm across. Note part of the hexapod ...
via Google News and Bing News