Molecular Nanoparticles of Ferric–Tannic Complexes Enhance Brain Magnetic Resonance Imaging and Activate Brain Clearance Pathways

Iron-containing drugs can be considered beneficial for noninvasive magnetic resonance imaging (MRI) and induction of essential biochemical processes. Herein, we present a new type of iron-containing drug based on molecular nanoparticles of ferric-tannic complexes (FTs), which could be used to enhance noninvasive brain MRI and modulate brain clearance pathways. Once intravenously administered to healthy Wistar rats, the maximum enhancement of the T1-weighted MRI signal was observed at 0.5 h postinjection, corresponding to their maximum accumulation in the brain. After this time, FTs were rapidly cleared by the brain, which was possibly modulated by organic anion transporters present at the blood-brain barrier. This result describes the "come-and-run" concept of FTs, which could be utilized as a brain-targeting agent for various purposes. Although the "come-and-run" mechanism allows them to have a short half-life in the brain, they remain long enough to activate brain clearance pathways such as autophagy, lysosomal function, and cellular clearance. Therefore, FTs could be considered new clinically translatable pharmaceuticals for brain MRI and the prevention of brain aging and related diseases.