Date of Award
1-1-2024
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Thomas A. Werfel
Second Advisor
Kristine L. Willett
Third Advisor
Joshua Sharp
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Nanoparticles (NPs) offer significant promise as drug delivery vehicles; however, their in vivo efficacy is often hindered by the formation of a protein corona (PC), which influences key physiological responses such as blood circulation time, biodistribution, cellular uptake, and intracellular localization. Understanding NP-PC interactions is crucial for optimizing NP design for biomedical applications. Traditional approaches have utilized hydrophilic polymer coatings like polyethylene glycol (PEG) to resist protein adsorption, but glycopolymer-coated nanoparticles have emerged as superior alternatives due to their biocompatibility and ability to reduce the adsorption of highly immunogenic proteins. In this study, we synthesized and characterized glycopolymer-based poly[2(diisopropylamino)ethyl methacrylate-b-poly(methacrylamidoglucopyranose) (PDPA-b-PMAG) NPs as an alternative to PEGylated NPs. We characterized the polymers using GPC, FT-IR, NMR, and the NPs using DLS and TEM. We assessed protein adsorption using SDS-PAGE and BCA assays and identified adsorbed proteins with LC-MS. The PMAG NPs were found to adsorb fewer proteins in vitro as well as fewer immunogenic proteins. Flow cytometry and confocal microscopy were employed to examine cellular uptake in RAW 264.7 macrophages and MDA-MB-231 tumor cells, where PMAG NPs showed higher uptake into tumor cells over macrophages. In vivo studies in BALB/c mice with 4T1 breast cancer cells showed that PMAG NPs exhibited prolonged circulation times and enhanced tumor accumulation compared to PEGMA NPs. The biodistribution analysis revealed greater selectivity for tumor tissue over the liver. These findings highlight the potential of glycopolymers NPs to improve tumor targeting and reduce macrophage uptake, offering significant advancements in cancer and immunotherapy. Our research establishes glycopolymer NPs as a promising platform for targeted and controlled tumor drug delivery.
Recommended Citation
Hulugalla, Kenneth Ryan, "Glycopolymeric Nanoparticles Enrich Less Immunogenic Protein Corona and Improve Tumor Delivery Compared to Pegylated Nanoparticles" (2024). Electronic Theses and Dissertations. 2944.
https://egrove.olemiss.edu/etd/2944