Date of Award

2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Engineering

First Advisor

Amber L. Doiron

Abstract

Nanomedicine holds incredible promise for clinical diagnostic and therapeutic applications. Nanoparticles (NPs) are widely used in this field due to the tunability of their characteristics, including size, shape, surface charge, and material composition. These customizable characteristics allow NPs to be effectively used in a variety of remedial applications. When NPs are administered within the body, they are exposed to a many different types of proteins that bind to their surface. These bound proteins heavily influence the biological response to the NPs. The NPs’ composition and surface chemistry determine the extent, as well as the specificity, of the proteins binding to the particle. Protein binding is one of the main determinants of bioavailability and biodistribution of NPs within the body; engineering the NP surface to direct the protein-particle interactions is crucial for therapeutic efficacy, as well as limiting toxicity.

To further investigate protein adsorption on NPs, polymeric NPs were synthesized with encapsulated fibroblast growth factor (FGF) using emulsion methods and were exposed to mouse serum for varying amounts of time (3 hours and 20 hours). FGF was chosen as the therapeutic agent because its intracellular delivery initiates a negative feedback loop that leads to reduced cancer cell migration and proliferation. To test the effects of particle composition and surface coatings, polylactic co-glycolic acid (PLGA) and alginate were used to generate two particle types, and polyethylene glycol (PEG) was separately included to form two additional particle types. Particle size and surface charge were measured after protein exposures, as well as the concentrations of protein existing within solution and on the NP surface. This study concluded that the use of PEG dramatically decreased the concentration of proteins adsorbed to the surface of PLGA NPs, cutting the number of proteins approximately in half. Additionally, the concentration of NPs and protein present in solution affect the protein adsorption kinetics, likely due to the changes in the number of interactions that take place and transport of proteins to the NP surface. As proteins bind to the surface of the particle, the particle hydrodynamic size increases slightly, which can clearly be seen after 20 hours of exposure. This new knowledge of material-specific protein adsorption for polymeric NPs that have encapsulated growth factor sheds light on the biological response likely seen when the FGF-encapsulating nanotechnology is translated in vivo for cancer treatment. Efficacious and controlled drug delivery for disease treatment depends heavily on the NP-protein complexes that form, and the interactions studied here create a solid foundation for a new potential cancer treatment.

Language

en

Number of Pages

110 p.

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