Synthesis and biodistribution of oligonucleotide-functionalized, tumor-targetable carbon nanotubes.
Single-wall carbon nanotubes (SWNT) show promise as nanoscale vehicles for targeted therapies. We have functionalized SWNT using regioselective chemistries to confer capabilities of selective targeting using RGD ligands, radiotracing using radiometal chelates, and self-assembly using oligonucleotides. The constructs contained approximately 2-7 phosphorothioate oligonucleotide chains and 50-75 amines per 100 nm length of SWNT, based on a loading of 0.01-0.05 mmol/g and 0.3-0.6 mmol/g, respectively. Dynamic light scattering suggested the functionalized SWNT were well dispersed, without formation of large aggregates in physiologic solutions. The SWNT-oligonucleotide conjugate annealed with a complementary oligonucleotide sequence had a melting temperature of 54 degrees C. Biodistribution in mice was quantified using radiolabeled SWNT-oligonucleotide conjugates. Appended RGD ligands allowed for specific binding to tumor cells in a flow cytometric assay. The techniques employed should enable the synthesis of multifunctional SWNT capable of self-assembly in biological settings.
Molecular Pharmacology and Chemistry Program and Departments of Medicine and Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Carlos H
CH
Villa
Michael R
MR
McDevitt
Freddy E
FE
Escorcia
Diego A
DA
Rey
Magnus
M
Bergkvist
Carl A
CA
Batt
David A
DA
Scheinberg
D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D037742:Nanotubes, Carbon; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry*; D014018:Tissue Distribution
D037742:Nanotubes, Carbon; D009841:Oligonucleotides