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

J. Justin Mulvey, Evan N. Feinberg, Simone Alidori, Michael R. McDevitt, Daniel A. Heller, David A. Scheinberg

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 (111)In-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.

Original languageEnglish (US)
Pages (from-to)4245-4255
Number of pages11
JournalInternational Journal of Nanomedicine
Volume9
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • 111In
  • azomethine
  • cycloaddition
  • DOTA
  • fullerene
  • thermophoresis

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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