Venue: CGFB Conference room
Chalermchai Pilapong
Assoc. Prof., Department of Radiologic Technology, Faculty of Associated Medical Science, Chiang Mai University, Thailand
Invited by Richard Ortega, LP2i
Title
Non-Invasive Brain Imaging and Modulation of Brain Clearance Pathways with Ferric-Tannic Nanocomplexes
Abstract
Currently, several diseases found in elderly people such as dementia cannot easily be cured because the treatments are usually performed in the late stage of the diseases. Much effort has made to explore new strategies for diagnosis, prevention, and treatment of the disease. We present herein a new technology to non-invasively image and modulate the cellular and molecular function of the brain. To develop such technology, we engineer molecular nanoparticle of ferric-tannic (FT) complexes to produce contrast change in T1 weighted MR imaging and to boost cellular clearance function and related pathways in the rat brain. Once intravenously administered into healthy Wistar rats, the maximum enhancement of the T1-weighted MRI signal was observed at 0.5 h post injection, corresponding to their maximum accumulation in the brain. After that time, FT was 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 FT, which could be utilised as brain-targeting agent for various proposes. 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 markers such as autophagic flux and LC3B. Moreover, experiments in primary cell cultures support that FT was capable of attenuating a potentially dangerous molecules (e.g. Aβ1–42) via activation of autophagy, lysosomal activity, and clearance. Concerning about toxicity of FT, FT was biodegradable and was found to have low acute toxicity, and have no sub-acute toxicity in Wistar rat without any abnormalities or lesions the cerebrum, cerebellum. Overall, our study might lead to the development of new clinically translatable pharmaceuticals for brain MRI imaging and controlling the function of cells inside the brain.
References
Kittilukkana A, Phatruengdet T, Intakhad J, Chariyakornkul A, Wongpoomchai R, Pilapong C. Molecular
Nanoparticles of Ferric-Tannic Complexes Enhance Brain Magnetic Resonance Imaging and Activate Brain Clearance Pathways. Anal Chem. 2022
Phiwchai I, Chariyarangsitham W, Phatruengdet T, Pilapong C*.
Ferric-Tannic Nanoparticles Increase Neuronal Cellular Clearance. ACS Chemical Neuroscience. 2019;10(9):4136-44.