Summary: | 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<sub>n</sub> = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho<sub>2</sub>O<sub>3</sub>) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho<sub>2</sub>O<sub>3</sub> 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<sub>2</sub>) of 13.1 and 9.9 s<sup>−1</sup>mM<sup>−1</sup>, respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r<sub>1</sub>) (i.e., 0.1 s<sup>−1</sup>mM<sup>−1</sup>) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R<sub>1</sub>) and transverse (R<sub>2</sub>) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T<sub>2</sub> MRI contrast agents in vitro.
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