Effects of Protein Corona on Gold Nanoparticle Cellular Uptake

Date of Award

12-2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Shikha Nangia

Keywords

Nanoparticles, Protein coronas

Subject Categories

Biomedical Engineering and Bioengineering

Abstract

Nanotechnology is a highly researched avenue for medical applications, especially for treatment of cancer. The size and nature of nanoparticles, specifically gold nanoparticles, make them a good candidate for targeted drug delivery vehicles in the body. However, a complication blocking the development of these drug delivery vehicles is that when gold nanoparticles are introduced to biological environments, they become rapidly covered with a protein corona. Once this corona forms on the nanoparticle, the nanoparticle-corona complex behave differently than the naked nanoparticle would behave. It is important for the progression of the use of nanoparticles in medical applications to understand the properties and behavior of these nanoparticle-corona complexes. The objective of this thesis work is to model gold nanoparticles and the protein coronas that form around them in order to better understand the nature of their behavior and interaction with cell membranes. This is done with a molecular dynamics modeling approach in order to bypass some of the limitations of physical study of nanoparticle-corona behavior. Pull simulations and umbrella sampling procedures were employed on six gold nanoparticle-corona complexes as they penetrate a cell membrane. The results indicate that rice-shaped nanoparticles are better suited for membrane translocation, even with the associated human blood serum protein corona. These results suggest that these negatively charged rice shaped gold nanoparticles are good contenders for future drug delivery vehicles. Future work needs to identify the make-up and progression of protein coronas as well as understand the mechanisms for cell membrane penetration of these nanoparticles and their protein coronas. Additionally, future work should succinctly establish the gold nanoparticle surface chemistry best conducive for drug delivery applications of gold nanoparticles. Many of these experiments can be performed computationally before being experimentally in vivo, and eventually in vivo.

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