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

Abstract 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).