Synthesis and Characterization of a Novel Biphenol-Based Gadolinium Complex for Encapsulation in Human Red Blood Cells

Gadolinium-based contrast agents are widely used in clinical magnetic resonance imaging (MRI) due to their strong paramagnetic properties and ability to enhance image contrast. Despite their diagnostic value, concerns remain regarding gadolinium toxicity and long-term tissue retention, particularly for less stable linear chelates. In this study, we report preliminary results on a newly synthesized gadolinium-based compound (L-Gd), in which the Gd3+ ion is coordinated to a specific ligand designed to improve biocompatibility. To evaluate the feasibility of L-Gd encapsulation within human RBCs (hRBCs) for drug delivery, its biocompatibility and cellular interactions were thoroughly investigated. RBCs represent an attractive biomimetic carrier system capable of limiting the direct exposure of tissues to paramagnetic agents while potentially improving circulation time and safety. In vitro assays demonstrated that L-Gd maintains high compatibility with hRBCs within specific concentration ranges, showing no significant hemolysis or morphological alterations. Furthermore, preliminary encapsulation studies indicate that L-Gd can be successfully associated with RBCs, supporting the potential of this approach for contrast agent delivery. These findings suggest that RBC-mediated transport of gadolinium complexes may represent a promising strategy to reduce toxicity and mitigate gadolinium retention. Further investigations will focus on optimizing encapsulation efficiency, relaxometric properties, and in vivo behavior of the L-Gd system.