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Issue 13, 2019
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Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices

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Abstract

The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using α3β4 nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional α3β4 nicotinic receptors on the cell membrane. The specific ligand binding to α3β4 nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets.

Graphical abstract: Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices

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Publication details

The article was received on 12 Feb 2019, accepted on 12 Mar 2019 and first published on 12 Mar 2019


Article type: Paper
DOI: 10.1039/C9NR01292C
Nanoscale, 2019,11, 6352-6359

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    Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices

    J. Sherwood, J. Sowell, N. Beyer, J. Irvin, C. Stephen, A. J. Antone, Y. Bao and L. M. Ciesla, Nanoscale, 2019, 11, 6352
    DOI: 10.1039/C9NR01292C

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