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New Nanoantibiotics destroy bacteria without Damaging healthy cells.

Antibiotic-resistant infection affect more than 2.8 million Americans each year, according to the Centers for Disease Control and Prevention, and more than 35,000 people die as a result of these infections.

To address this critical and global public health issue, a team of researchers led by Hongjun (Henry) Liang, Ph.D., from the Texas Tech University Health Sciences Center (TTUHSC) Department of Cell Physiology and Molecular Biophysics recently investigated whether a series of novel nanoparticles can kill some of the pathogens that cause human infection while causing no harm to healthy cells.

The work was published in Nature Communications on Jan. 11 and is titled "Hydrophilic Nanoparticles that Kill Bacteria while Sparing Mammalian Cells Reveal the Antibiotic Role of Nanostructures." Yunjiang Jiang, Ph.D., Wan Zheng, Ph.D., Keith Tran, Elizabeth Kamilar, Jitender Bariwal, Ph.D., and Hairong Ma, Ph.D., all from TTUHSC, were also part of the Liang team.

Hydrophobicity (a molecule's ability to repel water) and hydrophilicity (a molecule's ability to attract and dissolve in water) have been demonstrated to effect cells in the past; the more hydrophobic a chemical is, the more negative the reaction. However, there is no quantifiable criteria for how much hydrophobicity is acceptable, according to Liang.

"Basically, increasing hydrophobicity kills germs," Liang explained. "However, it will also harm healthy cells, which we do not want."

The Liang team used unique hydrophilic nanoparticles known as nanoantibiotics made by Liang's lab for their research. These new nanoantibiotics have the appearance of tiny hairy spheres, with multiple hydrophilic polymer brushes grafted onto silica nanoparticles of various sizes.

These synthetic chemicals, which Liang's lab makes, are designed to kill bacteria by disrupting membranes in the same way as antimicrobial peptides do, but in a different way that destroys bacterial membranes rather than mammalian cells. Antimicrobial peptides are a group of amphipathic molecules (partially hydrophilic, partly hydrophobic) that occur naturally and serve as the first line of defence for all multicellular organisms. The stability and toxicity of antimicrobial peptides limit their usage as antibiotics directly.

Researchers have grafted amphipathic molecules onto nanoparticles in previous investigations, and these, too, kill germs. However, according to Liang, the main problem with employing amphipathic molecules is that it's difficult to find the correct combination of hydrophobicity and hydrophilicity so that their toxicity to our own cells is considerably reduced.

"We eliminated that ambiguity in our instance since we started with a hydrophilic polymer," Liang explained. "Hydrophobic moieties' cytotoxicity is no longer an issue. Those hydrophilic polymers or silica nanoparticles by themselves are unable to kill bacteria; they must be grafted onto the nanostructure in order to do so. As a result, this is the first significant finding."

The size of the hairy spheres affects the degree of antibiotic activity, according to Liang, which is the research's second major finding. Those with a diameter of 50 nanometers or less appear to be substantially more active than those with a diameter greater than 50 nanometers. The ones sized around 10 nanometers, according to Liang, appear to be the most active. (The Liang team is able to identify the molecular mechanism of size-dependent antibiotic activity using synchrotron small angle x-ray scattering and other approaches.)

These findings are significant because killing bacteria using nanoantibiotics circumvents all known mechanisms of bacterial resistance unless bacteria fully redesign their cell membrane-making pathways, which Liang believes is implausible.

"It's also practically hard for bacteria to build new resistance to nanoantibiotics," said Liang. "Furthermore, this discovery provides a blueprint for developing novel antibiotics that kill bacteria on touch while remaining safe for humans because they are made with non-toxic and ecologically friendly chemicals."

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