Novel light-activated therapeutic nanoparticles, or “quantum dots,” eliminated up to 92% of drug-resistant bacterial cells and could be used as an alternative treatment option for infections, according to findings published in Nature Materials.
Nearly 2 million people in the United States are infected with antibiotic-resistant bacteria each year, resulting in at least 23,000 deaths, according to a 2013 CDC report. Moreover, antibiotic-resistant pathogens are increasing worldwide, and outbreaks caused by carbapenem-resistant Enterobacteriaceae (CRE), drug-resistant Clostridium difficile and drug-resistant Neisseria gonorrhoeae are frequently reported, according to Prashant Nagpal, PhD, assistant professor in the department of chemical and biological engineering at the University of Colorado Boulder, and colleagues.
“We are approaching a post-antibiotic era in which antibiotic treatments are no longer functional as a result of pandrug-resistant bacteria,” the researchers wrote. “Here we present a light-activated nano-therapeutic that inhibits [multidrug-resistant (MDR)] bacteria through targeted interactions with the cellular redox environment.”
The quantum dots, which are roughly 20,000 times smaller than a human hair and resemble electronic semiconductors, can interact within the cellular environment to kill bacteria, Nagpal said in a press release. Although several investigations found that gold, silver and other metal nanoparticles damaged healthy cells adjacent to infected cells, the green-emitting quantum dots can be tailored to target the infected cells due to their light-activated properties.
The quantum dots are only activated when exposed to light, allowing researchers to control wavelengths and target infected areas. When light is introduced, the quantum dots generate a redox-active species. The light-activated redox species (LARS) can then be induced to target MDR pathogenic bacteria.
“While we can always count on superbugs to adapt and fight the therapy, we can quickly tailor these quantum dots to come up with a new therapy and therefore fight back faster in this evolutionary race,” Nagpal said in the release.
During a recent investigation, Nagpal and colleagues exposed MDR clinical isolates and lab strains of Escherichia coli to cadmium telluride quantum dots with a bandgap of 2.4eV to examine the cellular response. Prior to activating illumination, no significant change was observed in cell growth. When light was activated, however, E. coli growth significantly decreased, possibly due to cell death, the researchers wrote. Eighty percent of cells were eliminated after 6 hours of treatment, and up to 92% of cells were killed after 8 hours of treatment with triple the nominal intensity.
The efficacy of quantum dots was further assessed using a low concentration of quantum dots and low light intensity in five clinical, MDR patient isolates previously found to be resistant to nine antibiotics. With the technology, growth was inhibited in a MRSA isolate by 29% (P = .015); a Klebsiella pneumoniae isolate expressing extended-spectrum beta-lactamases (ESBLs) by 59% (P = .017); two E. coli isolates by 83% and 64% (P = .005 and P = .0002); and a Salmonella typhimurium isolate by 56% (P = .003). Increasing the light intensity and/or quantum dot concentration resulted in a stronger therapy and further bactericidal effect, Nagpal told Infectious Disease News.
Based on these findings, the researchers concluded that with additional research, the technology may be used to treat topical infections and systemic infections during phototherapy. The spatial and temporal localization of the therapy may prevent adverse events typically associated with other treatment options, they wrote.
“Antibiotics are not just a baseline treatment for bacterial infections, but also used as a baseline therapy in immune compromised patients such as HIV and cancer patients,” co-researcher Anushree Chatterjee, PhD, assistant professor in the department of chemical and biological engineering at the University of Colorado Boulder, said in the release. “Failure to develop effective treatments for drug-resistant strains is not an option, and that’s what this technology moves closer to solving.” – by Stephanie Viguers
Disclosure: The researchers report filing a patent on quantum dot technology.