Abstract
A gadolinium-based contrast agent (GBCA) disulfide homodimer (Gd(3+)SS) has been incorporated into a lipoic acid (LA)-based hydrogel (Gd(3+)Gel) for enhanced magnetic resonance imaging (MRI). This study evaluates the magnetic properties and in vitro behavior of Gd(3+)Gel for potential applications in tracking internal injuries. Results indicate a direct shortening in the relaxation rate with greater magnitude of LA polymerization and a 2.8-fold enhancement in relaxivity (r(1)) at 1.4 T when Gd(3+)SS was conjugated into the hydrogel. This effect is attributed to a significant increase in the rotational correlation time (τ(r)) from 0.22 ± 0.05 ns (Gd(3+)SS) to 6 ± 1 ns (Gd(3+)Gel). Retention studies confirm that Gd(3+)SS remains covalently within the hydrogel, with retention of 64.7 ± 1.9% for Gd(3+)SS and 14.0 ± 1.4% for noncovalent binding gadoterate. The hydrogel relaxation rate (1/T(1)) increases from 1.1 to 3.5 s(-1) at 7 T from blank gel to Gd(3)(+)Gel (0.24 mM Gd(3+)). Cell studies show that PC3-PIP and RAW 264.7 cells maintain high viability with Gd(3+)SS but exhibit reduced viability with Gd(3+)Gel, consistent with known lipoic acid effects on immortalized cell lines. Cellular uptake studies using ICP-MS and confocal fluorescence microscopy confirm that monomeric Gd(3+)SS is readily internalized, whereas Gd(3+)Gel significantly limits diffusion and uptake. Rheology was conducted to determine the zero-shear viscosity of the LA hydrogel at various concentrations of LA. These findings suggest that the LA hydrogel scaffold enhances MRI contrast, minimizes leaching, and is easily injectable. Gd(3+)Gel is a promising tool for potential targeted imaging and controlled uptake during healing processes.