Renal-Targeted Inulin-Based Gd/Zn Hybrids for Safe MRI Contrast and Early Fibrosis Mitigation

Purpose: Gadolinium-based contrast agents (GBCAs), which are indispensable for magnetic resonance imaging (MRI), carry a severe risk of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD), particularly in those with advanced renal impairment. This critical safety concern necessitates the development of biocompatible alternatives that do not compromise diagnostic efficacy. Materials and Methods: Inulin-based nanoparticles (Inulin@Gd/Zn NPs) were synthesized by chelating inulin with gadolinium and zinc ions, aimed at being used as contrast agents that can replace conventional GBCAs. The morphology, size, and zeta potential of the nanoparticles were determined. The anti-fibrotic ability of Inulin@Gadolinium/zinc nanoparticles (Inulin@Gd/Zn NPs) was evaluated in vitro and in vivo, as well as their MRI imaging ability and metabolic performance in normal and fibrotic kidneys. A unilateral ureteral obstruction (UUO) model was created in mice and was used to evaluate the in vivo anti-fibrotic efficacy. Results: The ultra-small Inulin@Gd/Zn NPs (