The present work describes methods for fabricating multilayered core-shell nanoparticles composed of silica (SiO2) as a core, gadolinium compound (GdC) as an inner shell, and SiO2 as an outer shell (SiO2/GdC/SiO2) toward colloidally-stable, inert magnetic resonance imaging contrast agent, and for surface-modifying the SiO2/GdC/SiO2 nanoparticles toward immobilization of functional molecules on the SiO2/GdC/SiO2. SiO2 nanoparticles (particle size by transmission electron microscopy (TEM): 28.6±12.6 nm) were produced by a sol-gel method using tetraethylorthosilicate (TEOS) and methylamine in water/ethanol solution. GdC-coated SiO2 nanoparticles (SiO2/GdC) (GdC shell thickness by TEM: 35.9±4.9 nm) were synthesized by a homogeneous precipitation method using water/propanol solution containing the SiO2 nanoparticles, Gd(NO3)3, urea and polyvinylpyrrolidone. Succeeding SiO2coating of the SiO2/GdC nanaoparticles was performed by using TEOS and NaOH in the presence of SiO2/GdC nanoparticles. Consequently, SiO2/GdC/SiO2 nanoparticles (SiO2 shell thickness by TEM: 8.5±2.7 nm) could be obtained. The SiO2/GdC/SiO2 nanoparticles were successfully surface-modified by using 3aminopropyltrimethoxysilane for amination, and by followingly using succinic anhydride for carboxylation.

-The present work describes methods for fabricating multilayered core-shell nanoparticles composed of silica (SiO 2 ) as a core, gadolinium compound (GdC) as an inner shell, and SiO 2 as an outer shell (SiO 2 /GdC/SiO 2 ), and for surface-modifying the SiO 2 /GdC/SiO 2 nanoparticles. SiO 2 nanoparticles with an average size of 28.6±12.6 nm were produced by a sol-gel method using tetraethylorthosilicate (TEOS) and methylamine in water/ethanol solution. GdC-coated SiO 2 nanoparticles(SiO 2 /GdC) with an average particle size of 107.0±23.0 nm and an average GdC shell thickness of 35.9±4.9 nm were synthesized by a homogeneous precipitation method at 80°C in water/propanol solution containing Gd(NO 3 ) 3 , urea and polyvinylpyrrolidone in the presence of the SiO 2 nanoparticles. Succeeding SiO 2 -coating of the SiO 2 /GdC nanaoparticles was performed by using TEOS and NaOH in the presence of SiO 2 /GdC nanoparticles. Consequently, SiO 2 /GdC/SiO 2 nanoparticles with an average particle size of 119.0±39.0 nm and an average SiO 2 shell thickness of 8.5±2.7 nm could be obtained. The SiO 2 /GdC/SiO 2 nanoparticles were successfully surface-modified by using 3-aminopropyltrimethoxysilane for amination, and by followingly using succinic anhydride for carboxylation.