Ultrasmall, Water-Soluble Magnetite Nanoparticles with High Relaxivity for Magnetic Resonance Imaging

Ultrasmall (3, 4, 5, and 6 nm), water-soluble Fe₃O₄ magnetic nanoparticles were synthesized in diethylene glycol (DEG) via a facile one-pot reaction. Hydrodynamic size and relaxation time measurements did not show particle aggregation when Fe₃O₄ nanoparticles were dispersed in phosphate buffered saline, fetal bovine serum, or calf bovine serum for 1 week. Furthermore, the new Fe₃O₄ nanoparticles tolerated high salt concentrations (≤1 M NaCl) and a wide pH range from 5 to 11. Surface modification of the nanoparticles with poly(ethylene glycol) bis(carboxymethyl) ether (HOOC-PEG-COOH, 600 g/mol) was accomplished through a ligand-exchange reaction. The effects of PEG modification on magnetization and relaxivity of the Fe₃O₄ nanoparticles were investigated, and the results indicate that the increase in transverse relaxivity after PEG modification may be due to the increased volume of slowly diffusing water surrounding each nanoparticle. In vitro experiments showed that the DEG- and PEG-coated Fe₃O₄ nanoparticles have little effect on NIH/3T3 cell viability.