Identification of Toxin Inhibitors Using a Magnetic Nanosensor-Based Assay

    Authors

    O. J. Santiesteban; C. Kaittanis;J. M. Perez

    Comments

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    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

    WOS:000333538000022

    ISSN

    1613-6810

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