Bovine serum albumin (BSA) and cleaved-BSA conjugated ultrasmall Gd2O_3 nanoparticles: Synthesis, characterization, and application to MRI contrast agents

摘要

Bovine serum albumin (BSA) (M_n = 66.5kD, size = 14×4×4nm) is an attractive biological molecule for biomedical applications because of its water-solubility and bio-compatibility. It can also bind many ultrasmall nanoparticles (NPs) as confirmed in this study. We synthesized polyethylene glycol diacid (PEGD) coated ultrasmall Gd_2O_3 nanoparticles (PEGD-GNPs, the core d_(avg) = 2.0 nm), which were then conjugated to BSA and cleaved-BSA (C-BSA) (i.e. BSA-PEGD-GNPs and C-BSA-PEGD-GNPs) through amide bonding. Large relaxivities were observed in both aqueous sample solutions (r_1 =6.0s~(-1) mM~(-1) and r_2=28.0s~(-1)mM~(-1) for BSA-PEGD-GNPs and r_1 =7.6 s~(-1) mM~(-1) and r_2 = 22.0 s~(-1) mM~(-1) for C-BSA-PEGD-GNPs). Three tesla T_2 magnetic resonance imaging (MRI) in a mouse after the injection of an aqueous sample solution of BSA-PEGD-GNPs into a mouse tail vein revealed significant negative contrast enhancements. Large relaxivities and in vivo MR images prove that BSA-PEGD-GNPs and C-BSA-PEGD-GNPs are potential MRI contrast agents.