Size-Tunable, Ultrasmall NaGdF4 Nanoparticles: Insights into Their T1 MRI Contrast Enhancement

We report on the size-tunable synthesis of thermodynamically stable (beta) NaGdF4 nanoparticles (NPs) below 10 nm. Paramagnetic beta-NaGdF4 NPs of four different sizes (2.5-8.0 nm with a narrow size distribution) were synthesized by simple modifications of the reaction conditions affecting nanoparticle growth dynamics. The synthesized NPs were transferred to water by exchanging the oleate ligands with biocompatible polyvinyl-pyrrolidone, and analyzed for their ability to affect magnetic resonance (MR) T-1 longitudinal relaxivity at 1.5 T. The ionic relaxivity (unit Gd3+ concentration) values increased from 3.0 mM(-1) s(-1) to 7.2 mM(-1) s(-1) with decreasing particle size, and the relaxivity of the 2.5-nm particle is almost twice that of clinically used Gd-DTPA (Magnevist) relaxivity. The relaxivity per contrast agent (i.e., per nanoparticle) for these NPs is 200-3000 times larger than the clinical agent, showing great potential as local contrast enhancement probes. The rate of increase in ionic relaxivity with decreasing NP size was similar to the rate of increase in the NP surface-to-volume (Sly) ratio, giving direct indication that the surface Gd ions are the major contributors to the relaxivity enhancement. Further analysis based on concentration of NPs, mass concentration of NP, and unit surface area, has revealed that the surface Gd ions on a larger NP affect the relaxivity more strongly than those on a smaller NP. This is discussed based on the increase in NP rotational correlation time (tau(R)) with increasing size. A particular advantage of beta-NaGdF(4)NPs over other Gd3+-based inorganic NPs is that they are good hosts for upconverting emission. We demonstrate this by extending the synthesis protocol outlined here to prepare luminescent ultrasmall beta- NaGdF4:Yb3+/Tm3+ NPs as potential bimodal probes.