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Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes

Authors Mulvey JJ, Feinberg E, Alidori S, McDevitt M, Heller D, Scheinberg D

Received 12 April 2014

Accepted for publication 24 May 2014

Published 4 September 2014 Volume 2014:9(1) Pages 4245—4255

DOI https://doi.org/10.2147/IJN.S66050

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

J Justin Mulvey,1,2 Evan N Feinberg,1,3 Simone Alidori,1 Michael R McDevitt,4,5 Daniel A Heller,1,6 David A Scheinberg1,5,6

1Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA; 2Tri-Institutional MD-PhD Program, New York, NY, USA; 3Department of Applied Physics, Yale University, New Haven, CT USA; 4Department of Radiology and 5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 6Weill Cornell Medical College, New York, NY, USA

Abstract: We aimed to create a more robust and more accessible standard for amine-modifying single-walled carbon nanotubes (SWCNTs). A 1,3-cycloaddition was developed using an azomethine ylide, generated by reacting paraformaldehyde and a side-chain-Boc (tert-Butyloxycarbonyl)-protected, lysine-derived alpha-amino acid, H-Lys(Boc)-OH, with purified SWCNT or C60. This cycloaddition and its lysine adduct provides the benefits of dense, covalent modification, ease of purification, commercial availability of reagents, and pH-dependent solubility of the product. Subsequently, SWCNTs functionalized with lysine amine handles were covalently conjugated to a radiometalated chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The 111In-labeled construct showed rapid renal clearance in a murine model and a favorable biodistribution, permitting utility in biomedical applications. Functionalized SWCNTs strongly wrapped small interfering RNA (siRNA). In the first disclosed deployment of thermophoresis with carbon nanotubes, the lysine-modified tubes showed a desirable, weak SWCNT-albumin binding constant. Thus, lysine-modified nanotubes are a favorable candidate for medicinal work.

Keywords: fullerene, cycloaddition, azomethine, DOTA, thermophoresis, 111In

Erratum for this paper has been published

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