Peptide-Functionalized Layer-by-Layer Nanoparticles Demonstrate Improved Blood Brain Barrier Permeability for Glioblastoma Treatment
Name
ganesh-pganesh-sb-dmse-2023-thesis.pdf
Description
Thesis PDF
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4 MB
Format
Adobe PDF
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5395718aa0d7bafba40e5a9649148d4a
Author(s)
Ganesh, Priya
Advisor(s)
Hammond, Paula
Date Issued
June 2023
Publisher
Massachusetts Institute of Technology
Abstract
The greatest obstacle in the treatment of glioblastomas is the blood-brain barrier (BBB), the endothelial cells that line the vessels of the brain and are stitched together into a barrier by tight junction complexes. One approach to overcoming this barrier is encapsulating drugs in nanoparticles whose surfaces are engineered (usually, with the addition of ligands) to promote binding to various receptors of the BBB, thus triggering transcytosis and allowing the nanoparticle and its drug contents to cross the BBB. Previous research has shown that electrostatic absorption (as opposed to covalent functionalization) is a quick and effective method for attaching cationic, tumor-penetrating peptides to anionic nanoparticles synthesized through an iterative layer-by-layer (LbL) approach. Here, I demonstrate that LbL nanoparticles functionalized with Angiopep-2, a BBB-penetrating peptide, can penetrate the BBB to deliver their contents to the brain. Peptide-functionalized particles were screened in an in vitro transwell model of the blood-brain barrier, and particularly promising candidates were screened in a mouse model through intravital imaging, leading to a conclusion that the combination of a poly-L-aspartate outer layer and Angiopep-2 leads to significant improvement in nanoparticle uptake in the brain. Future work will include in vivo experiments with peptide-functionalized LbL nanoparticles with a hyaluronic acid (HA) outer layer, as HA particles have been shown to have in vivo transport properties not reflected in in vitro transport experiments.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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