Open AccessEnhanced MRI relaxivity of Gd 3+ ‐based contrast agents geometrically confined within porous nanoconstructs
Author(s) -
Sethi Richa,
Ananta Jeyarama S.,
Karmonik Christof,
Zhong Meng,
Fung Steve H.,
Liu Xuewu,
Li King,
Ferrari Mauro,
Wilson Lon J.,
Decuzzi Paolo
Publication year - 2012
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.1480
Subject(s) - mesoporous material , materials science , gadolinium , nanoparticle , nanoscopic scale , porosity , particle (ecology) , nanotechnology , chemical engineering , adsorption , nuclear magnetic resonance , analytical chemistry (journal) , chemistry , chromatography , composite material , oceanography , physics , geology , engineering , metallurgy , catalysis , biochemistry
Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd 3+ ‐based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H 2 O)] 2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~24 m m −1 s −1 for 5–10 nm pores and ~10 m m −1 s −1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer‐sphere compound, [GdTTHA] 3− , and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24 h of continuous agitation in phosphate‐buffered saline. These data support and confirm the hypothesis that the geometrical confinement of Gd 3+ ‐chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H 2 O)] 2− , and 4 times for [GdTTHA] 3− ) and, potentially, improved stability, reduced toxicity and tissue specificity. Copyright © 2012 John Wiley & Sons, Ltd.