Liver-Directing Fe(III)-Based MRI Contrast Agent

Liver cancer has been identified as the second most common cause of cancer-related mortality. Routine liver diagnosis by recording magnetic resonance (MR) images in the presence of a liver-directing contrast agent (CA) can recognize any abnormalities early. However, the clinically approved liver-specific Gd(III)-based CAs are of great concern for bio-safety. In fact, several medical agencies have restricted the usage of such CAs. Thus, to develop non-Gd-based biocompatible CAs for liver imaging, a thermodynamically stable and kinetically inert nonaquated six-coordinate paramagnetic Fe(III)-complex (1) is confined within a biocompatible porous silica nanoparticle of size about 18 nm. Such entrapment has boosted the longitudinal relaxivity value of Complex 1 (r₁ = 0.59 × 10^-3 m^-1s^-1) upto 9 times to 5.36 × 10^-3 m^-1s^-1, which further increased to 10.83 × 10^-3 m^-1s^-1 in the presence of 0.67 × 10^-3 m concentration of serum albumin protein. Surface functionalization of the nanoparticle with hydrophobic p-methoxybenzamide (C1@SiO₂-PMBA-NP) facilitates HepG2 cell internalization as evinced by in vitro fluorescent images and flow cytometry analyses. Time-dependent contrast changes in the liver MR images recorded on C57BL/6 mice in a preclinical MRI instrument establish the applicability of the biocompatible C1@SiO₂-PMBA-NP as the T₁-weighted liver-directing CA for magnetic resonance imaging (MRI).