Polyethylenimine-Coated Ultrasmall Holmium Oxide Nanoparticles: Synthesis, Characterization, Cytotoxicities, and Water Proton Spin Relaxivities.

Water proton spin relaxivities, colloidal stability, and biocompatibility of nanoparticle magnetic resonance imaging (MRI) contrast agents depend on surface-coating ligands. In this study, hydrophilic and biocompatible polyethylenimines (PEIs) of different sizes (M _n = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho ₂ O ₃ ) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho ₂ O ₃ nanoparticles, with an average particle diameter of 2.05 and 1.90 nm, respectively, demonstrated low cellular cytotoxicities, good colloidal stability, and appreciable transverse water proton spin relaxivities (r ₂ ) of 13.1 and 9.9 s ^-1 mM ^-1 , respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r ₁ ) (i.e., 0.1 s ^-1 mM ^-1 ) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R ₁ ) and transverse (R ₂ ) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T ₂ MRI contrast agents in vitro.