Investigation of the Interactions between Nanoparticles and Serum Proteins

dc.contributor.advisorCramb, David
dc.contributor.authorLi, Rui
dc.contributor.committeememberAnikovskiy, Max
dc.contributor.committeememberNoskov, Sergei
dc.contributor.committeememberPotter, Michael
dc.contributor.committeememberAlgar, W. Russ
dc.date2018-02
dc.date.accessioned2017-12-21T23:22:34Z
dc.date.available2017-12-21T23:22:34Z
dc.date.issued2017-12-18
dc.description.abstractNanoparticles (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.en_US
dc.identifier.citationLi, R. (2017). Investigation of the Interactions between Nanoparticles and Serum Proteins (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/5216
dc.identifier.urihttp://hdl.handle.net/1880/106220
dc.language.isoenen_US
dc.publisher.facultyScienceen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectnanoparticleen_US
dc.subjectprotein coronaen_US
dc.subjectnanoparticle-protein hybrid speciesen_US
dc.subjectfluorescence correlation spectroscopyen_US
dc.subjectquantum doten_US
dc.subject.classificationEducation--Sciencesen_US
dc.subject.classificationChemistry--Physicalen_US
dc.titleInvestigation of the Interactions between Nanoparticles and Serum Proteinsen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrue
ucalgary.thesis.checklistI confirm that I have submitted all of the required forms to Faculty of Graduate Studies. (See <a href="http://grad.ucalgary.ca/current/thesis/ethesis">http://grad.ucalgary.ca/current/thesis/ethesis</a> for more details)en_US
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