The Role of Physical Barrier Functions of Polyethylene Glycol Modified Nanoparticles in Modulating Their Blood Circulation
Open Access
- Author:
- Ben Mabrouk, Amira
- Graduate Program:
- Materials Science and Engineering
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- December 10, 2024
- Committee Members:
- Urara Hasegawa, Thesis Advisor/Co-Advisor
James Hansell Adair, Committee Member
John Mauro, Program Head/Chair
Scott H Medina, Committee Member - Keywords:
- drug delivery
PEGylation
liver endothelial cells
nanoparticle clearance.
Nanoparticles Clearance
Liver Endothelial cells
NMR Relaxometry
Drug Delivery - Abstract:
- Nanoparticles based drug delivery have garnered significant attention in medicine for their ability to deliver drugs at precise doses, enhance therapeutic outcomes, minimize side effects, and improve patient compliance. However, their rapid clearance, predominantly by the liver, remains a significant challenge. Upon administration, cells of the reticuloendothelial system (RES) swiftly sequester a substantial portion of the injected particles, regardless of their size, shape, or chemical composition. While Kupffer cells, liver residing macrophages, traditionally considered the primary contributors to nanoparticle clearance, recent evidence highlights the equally significant role of liver scavenger endothelial cells in this process. To address this challenge, surface modifications of nanoparticles have been extensively studied to modulate their interactions with biological systems. Among these strategies, PEGylation—grafting polyethylene glycol chains onto the particle surface—has emerged as a popular choice due to its hydrophilicity, biocompatibility, and proven ability to enhance nanoparticles performance in vivo. This thesis aims to explore the impact of the physical properties of surface-grafted methoxy polyethylene glycol chains (mPEG) on nanoparticle-cell interactions, with a focus on understanding their uptake by liver endothelial cells. We hypothesize that the mobility of surface mPEG, as a physical barrier function, modulates nanoparticles uptake by liver scavenger endothelial cells. Four groups of fluorescent polystyrene nanoparticles were modified with mPEG chains of varying molecular weights (2, 5, 10, and 20 kDa). Using NMR relaxometry, the relaxation rates of the mPEG canopy were measured, and chain mobility was estimated using the Bloembergen-Purcell model. Higher molecular weight mPEG was found to exhibit faster local motion compared to lower molecular weight chains. The nanoparticle groups were then evaluated in vitro using a cell model with functional similarities to liver scavenger endothelial cells. In vitro, nanoparticles with 20 kDa mPEG exhibited an 88% reduction in internalization by endothelial cells compared to those with 2 kDa mPEG. These findings elucidate the role of surface physical properties in modulating nanoparticles clearance, providing insights to optimize nanoparticles design for enhanced blood circulation.