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

Abstract

b S Supporting Information ' INTRODUCTIONColloidal nanomaterials show unique properties and are widely explored for a variety of applications. 1À4 Lanthanidebased nanomaterials have versatile utility in biological applications, as they can be made either as luminescent, magnetic, or as dual probe by selective doping of lanthanide ions. 5 In particular, paramagnetic Gd 3+ -doped NPs show tremendous potential as contrast agents (CAs) for magnetic resonance imaging (MRI). 6,7 MRI is a powerful medical diagnostic tool, where the relaxation of water protons exposed to an external magnetic field is used to obtain morphological and anatomical information with unlimited tissue penetration and yet high spatial resolution. 8 CAs are used to improve the sensitivity, because they interact with the surrounding water protons and shorten their relaxation time to provide better contrast. Two types of CAs are clinically prevalent: (i) paramagnetic Gd 3+ chelates, which affect the longitudinal relaxivity (r 1 ), and are termed positive (T 1 ) CAs, because they enhance the contrast; 9 and (ii) superparamagnetic iron oxide (SPIO) NPs, which affect transverse relaxivity (r 2 ) and are referred to as negative (T 2 ) CAs, because they diminish the signal intensity at the region of interest. 7,10 T 1 contrast agents are preferred over the T 2 agents as their enhanced brightening effect can easily be used to differentiate the signal from other pathogenic or biological conditions. 7 Gd 3+ chelates that are used clinically have very low body circulation time, because of their low molecular weight and show limitations as molecular probes for long-term tracking. 6 They also provide very low local contrast, because each chelate has only one Gd 3+ ion. To increase the local contrast and relaxivity, second-generation agents have been developed by covalently anchoring Gd 3+ chelates to different nanostructure frameworks, 11 or bundling multiple Gd 3+ chelates together using polymers, dendrimers, liposomes, and viral capsids. 12 These structures have been shown to have high relaxivity and increased local contrast as multiple Gd 3+ ions are coupled to a single nanostructure. The main disadvantage of this class of agents concerns their functionalization, which is tedious, expensive, and the number of ions that can be loaded to a NP is further limited by the number of anchoring sites available. Moreover, some of these aggregates are too large to be clinically useful. 6,7 Recently,

PEG-capped, lanthanide doped GdF3 nanoparticles: luminescent and T2 contrast agents for optical and MRI multimodal imaging

“…Experiments were carried out at 22 C using a Biospec Tomograph System (Bruker, Karlsruhe, Germany) equipped with a 4.7 T, 33 cm bore horizontal magnet (Oxford Ltd, UK) and with a gradient insert of 20 . The acquisition was segmented in 8 steps in order to obtain enough time resolution to monitor the recovery of the longitudinal magnetization.…”

Epitaxial growth of ultrathin layers on the surface of sub-10 nm nanoparticles: the case of β-NaGdF4:Yb/Er@NaDyF4 nanoparticles

“…Very recently, ultrasmall sized NaGdF 4 nanocrystals have exhibited great promise to serve as stable T 1 w MR contrast agents with a high T 1 w relaxivity and negligible leakage of free gadolinium ions. [39][40][41][42] When the ultrasmall sized NaGdF4 nanocrystals serve as a core to fabricate core-shell structured nanocomposites, it's reasonable that the T 1 w MR contrast performance should be affected due to the change in surface properties and less interaction with the surrounding protons. However, this remains unexplored.…”

Ligand-size and ligand-chain hydrophilicity effects on the relaxometric properties of ultrasmall Gd2O3 nanoparticles

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The studies conducted so far have investigated the relaxometric properties, surface functionalizations, and in vivo MR images of Gd 2 O 3 nanoparticles. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] A particle-size effect on the relaxometric properties of lanthanide oxide nanoparticles has been reported. 1,17,19 However, the effects of ligands on the relaxometric properties of ultrasmall Gd 2 O 3 nanoparticles have rarely been studied.…”