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

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 Phys...

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Autores principales:	Mulvey JJ, Feinberg EN, Alidori S, McDevitt MR, Heller DA, Scheinberg DA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ee052834584b4577bba271dd731710a6
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spelling	oai:doaj.org-article:ee052834584b4577bba271dd731710a62021-12-02T05:02:06ZSynthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes1178-2013https://doaj.org/article/ee052834584b4577bba271dd731710a62014-09-01T00:00:00Zhttp://www.dovepress.com/synthesis-pharmacokinetics-and-biological-use-of-lysine-modified-singl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 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, 111InMulvey JJFeinberg ENAlidori SMcDevitt MRHeller DAScheinberg DADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4245-4255 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Mulvey JJ Feinberg EN Alidori S McDevitt MR Heller DA Scheinberg DA Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
description	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
format	article
author	Mulvey JJ Feinberg EN Alidori S McDevitt MR Heller DA Scheinberg DA
author_facet	Mulvey JJ Feinberg EN Alidori S McDevitt MR Heller DA Scheinberg DA
author_sort	Mulvey JJ
title	Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
title_short	Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
title_full	Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
title_fullStr	Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
title_full_unstemmed	Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
title_sort	synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/ee052834584b4577bba271dd731710a6
work_keys_str_mv	AT mulveyjj synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes AT feinbergen synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes AT alidoris synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes AT mcdevittmr synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes AT hellerda synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes AT scheinbergda synthesispharmacokineticsandbiologicaluseoflysinemodifiedsinglewalledcarbonnanotubes
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Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes

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