title: Specific association of thiamine-coated gadolinium nanoparticles with human breast cancer cells expressing thiamine transporters.
abstract: Thiamine (vitamin B(1)) was investigated as a tumor-specific ligand for gadolinium nanoparticles. Solid nanoparticles containing gadolinium hexanedione (1.5 mg/mL) were engineered from oil-in-water microemulsion templates and coated with thiamine ligands. Thiamine ligands were synthesized by conjugating thiamine to either distearoylphosphatidylethanolamine (DSPE) or fluorescein via a poly(ethylene glycol) (PEG) spacer (Mw 3350). The efficiency of thiamine ligand attachment to nanoparticles was evaluated using gel permeation chromatography (GPC). Cell association studies were carried using a methotrexate-resistant breast cancer cell line, MTX(R)ZR75, transfected with thiamine transporter genes (THTR1 and THTR2). Thiamine-coated nanoparticle association with THTR1 and THTR2 cells was significantly greater than that with control breast cancer cells (MTX(R)ZR75 transfected with the empty expression vector pREP4) (p < 0.01; t-test). The nanoparticle cell association was significantly dependent on the extent of thiamine ligand coating on nanoparticles, expression of thiamine transporters in cells, temperature of incubation, and the concentration of competitive inhibitor (free thiamine). Further studies are warranted to assess the potential of the engineered thiamine-coated gadolinium (Gd) nanoparticles in neutron capture therapy of tumors.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: Moses O
authors.initials: MO
authors.lastname: Oyewumi
authors.forename: Shuqian
authors.initials: S
authors.lastname: Liu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Moscow
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mumper
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002850:Chromatography, Gel; D004655:Emulsions; D005079:Excipients; D005260:Female; D005682:Gadolinium / Q000737:chemistry* / Q000493:pharmacokinetics*; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008863:Microspheres; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D017785:Photons; D013831:Thiamine / Q000737:chemistry* / Q000493:pharmacokinetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004655:Emulsions; D005079:Excipients; D008024:Ligands; D026901:Membrane Transport Proteins; D010714:Phosphatidylethanolamines; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; C038089:1,2-distearoylphosphatidylethanolamine; D005682:Gadolinium; D013831:Thiamine