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
http://www.photonics.com/images/Web/Articles/2016/1/20/PIC_QD2.jpg
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 antibiotics1, 2, 3, 4. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific5, 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
a, Absorbance spectra for CdTe and CdSe of several sizes. Insets show transmission electron microscopy (TEM) images with colour-coded scale bars (50 nm except for CdTe-2.4, which is 25 nm). b, Scanning tunnelling spectroscopy (STS) meas…
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.