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Tissue-digging nanodrills do just enough damage

Molecule-sized drills do the damage they are designed to do. That’s bad news for disease.

Scientists at Rice University, Biola University and the Texas A&M Health Science Center have further validation that their molecular motors, light-activated rotors that spin up to 3 million times per second, can target diseased cells and kill them in minutes.

The team led by Biola molecular biochemist Richard Gunasekera and Rice chemist James Tour showed their motors are highly effective at destroying cells in three multicellular test organisms: worms, plankton and mice.

A study in the American Chemical Society journal ACS Applied Materials & Interfaces shows the motors caused various degrees of damage to tissues in all three species. The journal plans to designate the paper as an open-access ACS Editors’ Choice.

The project’s original goal was to target drug-resistant bacteria, cancer and other disease-causing cells and destroy them without damaging adjacent healthy cells. Tour has argued cells and bacteria have no possible defense against a nanomechanical drilling force strong enough to punch through their walls.

“Now it has been taken to a whole new level,” Tour said. “The work here shows that whole organisms, such as small worms and water fleas, can be killed by nanomachines that drill into them. This is not just single-cell death, but whole organism, with cell death in the millions.

“They can also be used to drill into skin, thereby suggesting utility in the treatment of things like pre-melanoma,” he said.

The researchers saw different effects in each of the three models. In the worm, C. elegans, the fast motors caused rapid depigmentation as the motors first caused nanomechanical disruption of cells and tissues. In the plankton, Daphnia, the motors first dismembered exterior limbs. In both cases, after a few days, most or all of the organisms died.

For mouse models, researchers applied the nanomachines in a topical solution to the skin. Activating the fast motors caused lesions and ulcerations, demonstrating their ability to function in larger animals.

“That mouse skin changes due to the ‘drilling’ by the nanomachines might be the one of most interesting aspects of the study to scientists,” said Gunasekera, an adjunct faculty member and former visiting scientist at Rice and currently associate dean and a professor of biochemistry at Biola. He is co-lead author of the paper with Thushara Galbadage, an associate professor of public health at Biola.

“It could mean direct topical treatment to skin conditions such as melanomas, eczema and other skin diseases,” Gunasekera said. “This paper is significant because it’s the first testing of nanomachines where we’ve proven its effectiveness in vivo. All other studies done so far were done in vitro.”

He suggested the motors could be used for therapeutic parasite control as well as local treatment of such diseases as skin cancer.

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Deadly ‘superbugs’ destroyed by molecular drills

Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

“These superbugs could kill 10 million people a year by 2050, way overtaking cancer,” Tour said. “These are nightmare bacteria; they don’t respond to anything.”

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

The researchers reported their results in the American Chemical Society journal ACS Nano.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

“Bacteria don’t just have a lipid bilayer,” Tour said. “They have two bilayers and proteins with sugars that interlink them, so things don’t normally get through these very robust cell walls. That’s why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect.”

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. “Sometimes, when the bacteria figures out a drug, it doesn’t let it in,” Tour said. “Other times, bacteria defeat the drug by letting it in and deactivating it.”

He said meropenem is an example of the former. “Now we can get it through the cell wall,” Tour said. “This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills.”

Gunasekera said bacterial colonies targeted with a small concentration of nanomachines alone killed up to 17% of cells, but that increased to 65% with the addition of meropenem. After further balancing motors and the antibiotic, the researchers were able to kill 94% of the pneumonia-causing pathogen.

Tour said the nanomachines may see their most immediate impact in treating skin, wound, catheter or implant infections caused by bacteria — like staphylococcus aureus MRSA, klebsiella or pseudomonas — and intestinal infections. “On the skin, in the lungs or in the GI tract, wherever we can introduce a light source, we can attack these bacteria,” he said. “Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria.”

“We are very much interested in treating wound and implant infections initially,” Cirillo said. “But we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis and tuberculosis, so we will also be developing respiratory infection treatments.”

Gunasekera noted bladder-borne bacteria that cause urinary tract infections may also be targeted.

The paper is one of two published by the Tour lab this week that advance the ability of microscopic nanomachines to treat disease. In the other, which appears in ACS Applied Materials Interfaces, researchers at Rice and the University of Texas MD Anderson Cancer Center targeted and attacked lab samples of pancreatic cancer cells with machines that respond to visible rather than the previously used ultraviolet light. “This is another big advance, since visible light will not cause as much damage to the surrounding cells,” Tour said.

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Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

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