Multianchored Glycoconjugate-Functionalized Magnetic Nanoparticles: A Tool for Selective Killing of Targeted Bacteria via Alternating Magnetic Fields

2017 
New technologies that do not rely on antibiotics are urgently needed to treat bacterial infections caused by multidrug-resistant bacteria. Herein, the feasibility of using alternating magnetic field (AMF) to selectively kill enterotoxigenic Escherichia coli strain K99 (EC K99) in the presence of multianchored glycoconjugate-functionalized magnetic nanoparticles is explored. Poly(ethylene oxide)-poly(acrylic acid)-dopamine functionalized magnetic nanoparticles (PEO-MNPs) are synthesized and functionalized with bacteria-specific glycoconjugate Neu5Ac(α2-3)-Gal-(β1-4)Glcβ-sp (GM3-MNPs) for specific adherence to EC K99. When such mixtures are exposed to an alternate magnetic field (31 kA m−1, 207 KHz), an ≈3-log reduction in colony forming units of EC K99 is achieved in 120 min. Moreover, in a mixed-bacterial culture environment, targeted killing of EC K99 is achieved with minimal damage to nontargeted bacterium. Electron microscopy images along with live/dead staining assays demonstrate visible membrane damage of EC K99 cells in the presence of GM3-MNPs and AMF. Additionally, intracellular adenosine triphosphate (ATP) levels of EC K99 are significantly diminished in the presence of GM3-MNPs and AMF. These results suggest that specific glycoconjugate-functionalized magnetic nanoparticles when mediated by AMF can be potentially used as a novel nonantibiotic treatment platform to inactivate/kill targeted bacterial pathogens, with minimal impact on normal microflora and the affected body region/tissue.
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