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Functionalized carbon nanotubes have already demonstrated great biocompatibility and potential for drug delivery. We have synthesized acid oxidized and non-covalently PEGlyated single-walled carbon nanotubes (SWNTs), which were previously prepared for drug delivery purposes, and explored their potential for detoxification in the bloodstream. Our investigations of the binding of SWNTs to a pore-forming toxin pyolysin show that SWNTs prevented toxin-induced pore formation in the cell membrane of human red blood cells. Quantitative hemolysis assay and scanning electron microscopy were used to evaluate the inhibition of hemolytic activity of pyolysin. According to Raman spectroscopy data, human red blood cells, unlike HeLa cells, did not internalize oxidized SWNTs. Molecular modeling and circular dichroism measurements were used to predict the 3-D structure of pyolysin (domain 4) and its interaction with SWNTs. The tryptophan-rich hydrophobic motif in the membrane-binding domain of pyolysin, a common construct in a large family of cholesterol-dependent cytolysins, shows high affinity for SWNTs.


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Carbon Nanotubes Inhibit the Hemolytic Activity of the Pore-Forming Toxin Pyolysin

Show Author's information Apraku David DonkorZhengding SuHimadri S. MandalXu JinXiaowu (Shirley) Tang( )
Department of ChemistryUniversity of WaterlooWaterlooON N2L 3G1Canada

Abstract

Functionalized carbon nanotubes have already demonstrated great biocompatibility and potential for drug delivery. We have synthesized acid oxidized and non-covalently PEGlyated single-walled carbon nanotubes (SWNTs), which were previously prepared for drug delivery purposes, and explored their potential for detoxification in the bloodstream. Our investigations of the binding of SWNTs to a pore-forming toxin pyolysin show that SWNTs prevented toxin-induced pore formation in the cell membrane of human red blood cells. Quantitative hemolysis assay and scanning electron microscopy were used to evaluate the inhibition of hemolytic activity of pyolysin. According to Raman spectroscopy data, human red blood cells, unlike HeLa cells, did not internalize oxidized SWNTs. Molecular modeling and circular dichroism measurements were used to predict the 3-D structure of pyolysin (domain 4) and its interaction with SWNTs. The tryptophan-rich hydrophobic motif in the membrane-binding domain of pyolysin, a common construct in a large family of cholesterol-dependent cytolysins, shows high affinity for SWNTs.

Keywords: Single-walled carbon nanotubes(SWNT), pore-forming toxin, pyolysin, hemolytic activity, red blood cell, protein-nanotube interaction, detoxification

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Received: 19 November 2008
Revised: 31 March 2009
Accepted: 13 April 2009
Published: 01 July 2009
Issue date: July 2009

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© Tsinghua University Press and Springer-Verlag 2009

Acknowledgements

Acknowledgements

The authors would like to thank D. Weber for assistance with SEM measurements, Lisa Pokrajac and Dr. M. Palmer for PLO production and purification, and Dr. J. F. Honek for assistance in molecular modeling. This work was supported by Dr. Tang's startup fund from University of Waterloo and by grants from the Natural Science and Engineering Research Council (NSERC) of Canada.

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