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Quantum dots target infections

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Photoactivated QDs Kill Antibiotic-Resistant ‘Superbugs’

BOULDER, Colo., Jan. 20, 2016 — A technique for treating bacterial infections has successfully used light-activated quantum dots (QDs) to kill multiple multidrug-resistant strains.

http://www.photonics.com/Article.aspx?AID=58218

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Modified atomic force micrograph of multidrug-resistant E. coli. Courtesy of the Nagpal Group/University of Colorado Boulder.

The approach is adaptive to constantly evolving drug-resistant bacteria and avoids damage to surrounding cells, an issue encountered in earlier attempts that deployed metal nanoparticles such as gold and silver to combat bacteria.

“By shrinking these [QD] semiconductors down to the nanoscale, we’re able to create highly specific interactions within the cellular environment that only target the infection,” said professor Prashant Nagpal of the University of Colorado Boulder.

The QDs — which are inactive in darkness — were tailored to target particular infections thanks to their light-activated properties. The researchers said that by modifying the wavelength of light applied, they could activate the QDs to alter and kill infected cells with specificity.

Napgal and his team tested the QD therapy on mammalian tissue containing bacterial cells in mono- and cocultures. The bacteria under investigation were ethicillin-resistant Staphylococcus aureus, carbapenem-resistant E. coli, and extended-spectrum ß-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium.

They reported 92 percent of bacterial cells were killed, while leaving mammalian cells intact. The QDs could also be tuned to increase bacterial proliferation.

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Plated antibiotic resistant ‘superbugs’ before and after treatment with nanoparticles. Courtesy of the Nagpal Group/University of Colorado Boulder.

The team said the killing effect was independent of the QD material used; rather, it was controlled by the redox potentials of the photogenerated charge carriers, which selectively altered cellular redox states. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections, the researchers said.

The specificity of the treatment could help reduce or eliminate the potential side effects of other treatment methods, as well as provide a path forward for future development and clinical trials.

“Antibiotics are not just a baseline treatment for bacterial infections, but HIV and cancer as well,” said professor Anushree Chatterjee. “Failure to develop effective treatments for drug-resistant strains is not an option, and that’s what this technology moves closer to solving.”

Nagpal and Chatterjee are the cofounders of Praan Biosciences Inc., a startup that can sequence genetic profiles using a single molecule, and have filed a patent on the QD therapy technology.

The research was published in Nature Materials (doi: 10.1038/nmat4542).

Photoexcited quantum dots for killing multidrug-resistant bacteria

Colleen M. Courtney, Samuel M. Goodman, Jessica A. McDaniel, Nancy E. Madinger, Anushree Chatterjee, Prashant Nagpal

Nature Materials(2016)      http://dx.doi.org:/10.1038/nmat4542

Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics^{1, 2, 3, 4}. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific^{5, 6, 7, 8}. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producingKlebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

Figure 2: The effect of CdTe-2.4 is specific to the reduction and oxidation potentials.close