Investigation of the Interactions between Nanoparticles and Serum Proteins
Date
2017-12-18
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Abstract
Nanoparticles (NPs) are promising tools in biomedical applications due to their small size and unique properties. Once a NP enters the biological milieu, it encounters a variety of biomolecules, such as proteins, lipids, and nucleic acids. The “decoration” of the NP surface with proteins is described as the formation of a “protein corona”, which is known to alter the original identity, biofunctionality, and nanotoxicity of the NPs. The interactions between NPs and proteins have been extensively studied for decades, but the mechanism is still not fully understood due to the complexity and dynamics of the formation of the NP-protein complexes, thereby greatly hindering the NP practical clinical applications.
In the studies described in this thesis, we examined the interactions between quantum dots (QDs) and serum proteins with the use of two-photon excitation fluorescence cross-correlation spectroscopy (TPE-FCCS). We aim to explore the QD-protein interactions both thermodynamically and kinetically, so as to gain an insight into the formation mechanism of the QD-protein complexes. Our results suggest a limited number of binding spots on QD surface available for serum protein adsorption. In addition, two different types of binding spots with different binding priorities were discovered. The nature (i.e., hydrophobicity and specific/non-specific binding sites) of the two binding spots is likely to be different such that various proteins (i.e., serum albumins and globulins) may interact with the two binding spots due to different predominant driving forces (i.e., electrostatic interactions and hydrophobic effects). The effect of the preceding protein adsorption on the subsequent QD-protein interactions was also found to be dependent on the types of the pre-occupied binding spots as well as the types of the pre-coating proteins. Furthermore, our results indicate an irreversible formation of a hybrid QD-protein species, which is not only interesting but also significant as it challenges the common perception of the formation of a protein corona monolayer around the NP surface. We believe our studies greatly help broaden the understanding of the NP-protein interactions, especially for NPs with a small size (diameter ≤ 10 nm) and/or a non-uniform surface with limited binding spots available for protein adsorption.
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Keywords
nanoparticle, protein corona, nanoparticle-protein hybrid species, fluorescence correlation spectroscopy, quantum dot
Citation
Li, R. (2017). Investigation of the Interactions between Nanoparticles and Serum Proteins (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.