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

Abstract

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 T 1-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.

Early Detection of Hepatocarcinogenicity in Rats Using MRI with Ferric–Tannic Nanoparticles

“…In addition, XRF was used to determine the distribution of iron in liver tissue. 24 Typical XRF Fe maps of the FFPE liver of control and DENinduced rats after being injected with FT NPs are shown in Figure 3f. A stronger Fe signal can be seen in DEN-induced groups at week 9 and week 16 of induction compared to the respective control groups and the DEN-induced group at week 5 of induction.…”

“…A similar trend was observed in the iron staining: a higher intensity was found in DEN-induced groups at week 9 and week 16 of induction compared to that in control groups and the DEN-induced group at week 5 of induction (Figure e). In addition, XRF was used to determine the distribution of iron in liver tissue . Typical XRF Fe maps of the FFPE liver of control and DEN-induced rats after being injected with FT NPs are shown in Figure f.…”

“…FT NPs have been shown to produce a contrast change in T 1 -weighted MRI by enhancing the longitudinal relaxation rate of water protons. , The procedure for producing FT NPs along with their physicochemical properties, reported in detail in our previous works, , has shown their commercial and clinical feasibility. Herein, at first, we aimed to determine whether FT could enhance MRI contrast in the liver of rats having cancerous lesions in comparison with a commercially available GBCA, Primovist (BAYER).…”

“…The XRF analysis was carried out according to our previous work with some modifications . A Horiba XRF analyzer was used to determine the iron content in the liver.…”

“…The XRF analysis was carried out according to our previous work with some modifications. 24 A Horiba XRF analyzer was used to determine the iron content in the liver. In a typical experiment, FFPE liver tissue was scanned with the following parameters: live time, 400 s; processing time, P4; X-ray tube voltage, 30 kV; XGT diameter, 1.2 mm; and current, 1.0 mA.…”