A new biocompatible amino-Gd-metallofullerenol (Amino-Gd-FulOH) nanoplatform as a potential MRI contrast agent and its effect on macrophages

Endohedral gadolinium-containing metallofullerenols are promising multifunctional nanomaterials with low cytotoxicity and strong imaging capabilities. Structurally organized at atomic, molecular, and supramolecular levels, these nanoparticles have attracted attention for their ability to serve as drug carriers, contrast agents for MRI, and potential radioprotectors in oncology. Despite growing interest, their molecular mechanisms of action remain insufficiently understood. In our study, we investigated the effects of new compound amino-Gd-metallofullerenol (amino-Gd-FulOH) on the functions of macrophages, a key component of both the tumor and immune responses. Amino-Gd-FulOH exhibited no significant impact on macrophage motility, adhesion, and expression of key cytoskeletal regulators RhoA, Rock2, and Pak1 proteins. However, it altered the expression and localization of vinculin, a cytoskeletal protein involved in focal adhesion. Additionally, at higher concentrations, amino-Gd-FulOH induced dose-dependent apoptosis and modest alterations of the cell cycle. MRI analysis showed that amino-Gd-FulOH significantly enhanced T₁-weighted signal intensity in macrophages compared to untreated controls, with a signal comparable to the clinical Gd-based agent Dotarem. Under these conditions, amino-Gd-FulOH exhibits a markedly higher apparent molar relaxivity than Dotarem, providing strong evidence that, per mole of Gd, our compound demonstrates superior relaxation efficiency. While it modulates macrophage viability in dose-dependent manner, it preserves basic functions such as adhesion and migration. The combination of functional biocompatibility, rapid post-labeling clearance, and high imaging utility underscores its potential as a safe and effective theranostic compound, warranting further mechanistic exploration.