A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging

Abstract

Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.

Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications

“…There are many visualization procedures exist for imaging of nanoliposomes, For instance to detect particles bigger than 290 nm and impurity with larger particles, a phase contrast optical microscope is an appropriate choice (Gaidukevich et al 2016) and a polarizing microscope is suitable for revealing lamellarity of liposomes (Tanifum et al 2016). Scanning electron microscopy, freeze-fracture, and negative staining are common techniques applied to characterize nanoliposome structures.…”

Phyto-Therapeutic and Nanomedicinal Approaches to Cure Alzheimer’s Disease: Present Status and Future Opportunities

“…They showed that the synthesized NPs were biocompatible and biologically active with the potential of being used for early detection of AD ( Yin et al, 2015 ). Similarly, in another study, Tanifum et al (2016) reported the synthesis of amyloid fibril-binding ligand ET6-21. The ligand was used to prepare amyloid-targeted liposomes, tagged with Gd chelates and indocyanine green for visualization by magnetic resonance imaging (MRI) and infrared microscopy, respectively.…”

Alzheimer’s disease is getting easier to spot

“…Working with Jason Eriksen, a neuroscientist at the University of Houston, the team has shown that, in mice, the nanoparticle -which contains a contrast dye used for diagnosing tumours of the brain and spinal cord -can cross the blood-brain barrier to reach the brain, where it binds to amyloid-β deposits (pictured, green) and emits a signal when scanned using the low-field strength MRI machines that are commonly found in clinics 8 .…”