title: Synthesis, pharmacokinetics, and biological use of lysine-modified single-walled carbon nanotubes.
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.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Tri-Institutional MD-PhD Program, New York, NY, USA.
authors.forename: J Justin
authors.initials: JJ
authors.lastname: Mulvey
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Department of Applied Physics, Yale University, New Haven, CT USA.
authors.forename: Evan N
authors.initials: EN
authors.lastname: Feinberg
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Alidori
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: McDevitt
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Weill Cornell Medical College, New York, NY, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Heller
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA ; Weill Cornell Medical College, New York, NY, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D061565:Cycloaddition Reaction / Q000379:methods*; D005260:Female; D037741:Fullerenes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007205:Indium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008239:Lysine / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D037742:Nanotubes, Carbon / Q000737:chemistry*; D034741:RNA, Small Interfering; D013696:Temperature; D013882:Thiosemicarbazones / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D001391:Azo Compounds; D037741:Fullerenes; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering; D013882:Thiosemicarbazones; C512188:azomethine; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008239:Lysine; C069837:fullerene C60
keywords: 111In; DOTA; azomethine; cycloaddition; fullerene; thermophoresis