Fluorescent PLGA-CY5 from PolySciTech used in development of layer-by-layer nanoparticles as analytical tools for understanding the blood-brain-barrier

 

Unlike most organs in the human body, the brain has a significant barrier against uptake of medicinal compounds present in the blood. Crossing this barrier is difficult for anything other than small, hydrophobic molecules and is particularly challenging for nanoparticles. This barrier is poorly understood and the exact features and properties of a particle which allow it to either pass or, not pass, through the barrier has not been fully characterized. Researchers at Massachusetts Institute of Technology used PLGA-CY5 (cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fluorescently trackable nanoparticles. They tested these particles with a variety of configurations and surface chemistries against model brain barrier systems to further understand what properties control this transport. This research holds promise to improve delivery of therapeutics to the brain in the future. Read more: Lamson, Nicholas G., Andrew J. Pickering, Jeffrey Wyckoff, Priya Ganesh, Joelle P. Straehla, and Paula T. Hammond. "Core material and surface chemistry of Layer-by-Layer (LbL) nanoparticles independently direct uptake, transport, and trafficking in preclinical blood-brain barrier (BBB) models." bioRxiv (2022). https://www.biorxiv.org/content/10.1101/2022.10.31.514595.abstract

“Development of new treatments for neurological disorders, especially brain tumors and neurodegenerative diseases, is hampered by poor accumulation of new therapeutic candidates in the brain. Drug carrying nanoparticles are a promising strategy to deliver therapeutics, but there is a major need to understand interactions between nanomaterials and the cells of the blood-brain barrier (BBB), and to what degree these interactions can be predicted by preclinical models. Here, we use a library of eighteen layer-by-layer electrostatically assembled nanoparticles (LbL-NPs) to independently assess the impact of nanoparticle core stiffness and surface chemistry on in vitro uptake and transport in three common assays, as well as intracellular trafficking in hCMEC/D3 endothelial cells. We demonstrate that nanoparticle core stiffness impacts the magnitude of material transported, while surface chemistry influences how the nanoparticles are trafficked within the cell. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice, and we discover that a hyaluronic acid surface chemistry provides an unpredicted boost to transport. Taken together, these findings highlight the importance of considering factors such as assay geometry, nanomaterial labelling strategies, and fluid flow in designing preclinical assays to improve nanoparticle screening throughput for drug delivery to the brain.”

See Video: https://youtu.be/fAHFUmqonmc