TTUHSC scientist receives US patent to produce new nanoantibiotics

According to the Centers for Disease Control and Prevention, more than 2.8 million Americans contract antibiotic-resistant bacterial infections each year, and approximately 35,000 of these patients do not survive their infection.

In his quest to find solutions to the problem of antibiotic resistance, Hongjun (Henry) Liang, Ph.D., of the Department of Cellular Physiology and Molecular Biophysics at Texas Tech University Health Sciences Center (TTUHSC), focused his research on the development of new nanoparticles. known as nanoantibiotics that target bacterial infections, especially those resistant to treatment with known antibiotics.

To date, Liang’s work has resulted in several peer-reviewed publications and, as of July 26, a U.S. patent titled “HydrophilicNanostructured Membrane Active Antimicrobials With High Activity, Selectivity And Biodegradability”, which enables the Liang laboratory team to produce the new nanoantibiotics. .

Many antibiotics are already used in clinics, and many of them are quite effective against ordinary infections. But we face this growing challenge with MRSA (methicillin-resistant staphylococcus aureus) and other types of drug-resistant bacteria, which are the bacteria that turn ordinary infections into life-threatening events. »


Hongjun (Henry) Liang, Ph.D., Department of Cellular Physiology and Molecular Biophysics at Texas Tech University Health Sciences Center (TTUHSC)

Liang hopes to establish a new generation of antibiotics that have three characteristics: they can kill bacteria without toxicity to healthy cells, they are biodegradable and environmentally degradable so as not to harm normal microbial communities in natural habitats, and they are less likely to induce resistance.

Previous research has shown that a molecule’s ability to repel water (hydrophobicity) and its ability to attract and dissolve in water (hydrophilicity) have a significant effect on cells. Liang said the more hydrophobic a substance is, the worse the reaction it will cause. However, he added, there is no quantitative standard for the acceptable degree of hydrophobicity.

“Basically, you can kill bacteria when you increase hydrophobicity,” Liang said. “But it will also kill healthy cells, and we don’t want that.”

In a study published in January 2022 by Nature Communication, the Liang team developed new hydrophilic nanoantibiotics that looked like tiny hairy spheres composed of many hydrophilic polymer brushes grafted onto silica nanoparticles of different sizes. These synthetic compounds, which Liang’s lab also produces, are designed to kill bacteria via membrane disruption using a different mode of membrane remodeling that damages bacterial membranes while leaving mammalian cells intact.

This study was the third published by the Liang laboratory on the subject of nanoantibiotics. The first and second papers that elucidated the design concept of hydrophilic nanoantibiotics were published by ACS Infectious Disease in 2017 and Biomacromolecules in 2020. Both were featured as a cover article in their respective journal and highlighted by Chemical & Engineering News.

Armed with the three published studies and the patent, Liang said his team is now focusing on a two-pronged approach to developing and refining the nanoantibiotics for use in patients.

The first prong, which Liang described as the research and academic side of his effort, is to push for clinical trials. To start this process, the Liang lab will apply for additional federal grants that support animal studies and eventually lead to clinical trials in human patients.

“It’s more like the research and academic side of our efforts,” Liang added.

The second part of Liang’s approach is to work with the Texas Tech University Innovation Hub to help commercialize his lab’s invention.

“By taking advantage of the research commercialization training opportunity of our innovation center, we hope to identify interested parties from the pharmaceutical industry who are able or willing to collaborate with us,” Liang said. “One of our likely directions is to apply for a Small Business Innovation Research (SBIR) grant for pilot-scale production. That’s our two-pronged approach.”

Liang said the infection poses a significant challenge for frontline doctors and scientists. It is a challenge that he wants to be able to meet by using innovation to develop a new generation of antibiotics.

“That’s our goal and we’re on track to achieve it,” Liang said. “I can’t say this is the only way forward; of course, there are many different ways. The novelty of our contribution is to address this challenge by designing antibiotics from a nano- engineering. This is a whole new avenue that is not well explored, and we are proud of our progress so far.”

Source:

Texas Tech University Health Sciences Center

Irene B. Bowles