Title
Identification of Toxin Inhibitors Using a Magnetic Nanosensor-Based Assay
Abbreviated Journal Title
Small
Keywords
magnetic nanosensors; iron oxide; drug repurposing; anthrax; toxins; ANTHRAX LETHAL FACTOR; SULINDAC SULFONE; RELAXATION; SUSCEPTIBILITY; NANOPARTICLES; CELLS; Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &; Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter
Abstract
A magnetic nanosensor-based method is described to screen a library of drugs for potential binding to toxins. Screening is performed by measuring changes in the magnetic relaxation signal of the nanosensors (bMR nanosensors) in aqueous suspension upon addition of the toxin. The Anthrax lethal factor (ALF) is selected as a model toxin to test the ability of our bMR nanosensor-based screening method to identify potential inhibitors of the toxin. Out of 30 molecules screened, sulindac, naproxen and fusaric acid are found to bind LF, with dissociation constants in the low micromolar range. Further biological analysis of the free molecules in solution indicate that sulindac and its metabolic products inhibited LF cytotoxicity to macrophages with IC50 values in the micromolar range. Meanwhile, fusaric acid is found to be less effective at inhibiting LF cytotoxicity, while naproxen does not inhibit LF toxicity. Most importantly, when the sulindac and fusaric acid-bMR nanosensors themselves are tested as LF inhibitors, as opposed to the corresponding free molecules, they are stronger inhibitors of LF with IC50 values in the nanomolar range. Taken together, these studies show that a bMR nanosensors-based assay can be used to screen known drugs and other small molecules for inhibitor of toxins. The method can be easily modified to screen for inhibitors of other molecular interactions and not only the selected free molecule can be study as potential inhibitors but also the bMR nanosensors themselves achieving greater inhibitory potential.
Journal Title
Small
Volume
10
Issue/Number
6
Publication Date
1-1-2014
Document Type
Article
Language
English
First Page
1202
Last Page
1211
WOS Identifier
ISSN
1613-6810
Recommended Citation
"Identification of Toxin Inhibitors Using a Magnetic Nanosensor-Based Assay" (2014). Faculty Bibliography 2010s. 6039.
https://stars.library.ucf.edu/facultybib2010/6039
Comments
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