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.