Document Type

Thesis

Date of Award

5-31-2024

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering

First Advisor

Kathleen McEnnis

Second Advisor

Rajarshi Chattaraj

Third Advisor

Maryam Hajfathalian

Abstract

Due to high specificity and less toxicity, nanoparticles have become promising for targeted drug delivery against cancer, although they face challenges when they enter the bloodstream, making their behavior unpredictable. The deposition of proteins on nanoparticles, the protein corona, changes their biosignature, affecting their circulation, drug release potency, targeting ability, and immunogenicity. The continuous exchange of protein layers on a nanoscale is complex to analyze.

Nanoparticle tracking analysis (NTA) is a method to characterize nanoparticles in blood plasma by combining principles of light scattering microscopy and Brownian motion. In this work, time-dependent experiments with plasma were conducted to analyze the effect of anticoagulants and types of animal species on protein corona formation. The anticoagulants were found to not affect protein corona formation, although they may be responsible for aggregation. The difference in protein composition between species affects corona formation. Increasing plasma concentration increased competitive binding, giving thicker protein coronas. It is observed that salt molarity affects protein corona formation and depends on plasma build up of species. The binding affinity of proteins decreased corona formation at higher speeds. Surface modification using PEG reduces protein corona formation and aggregation. Protein-based biointerfaces were added using physical and chemical adsorption methods, showing promising results for attaching albumin-based structures on nanoparticles for targeted drug delivery.

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