Date of Award

6-1-2019

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2019

Department

Bioengineering

Abstract

When engineered nanoparticles (NPs) enter into a biological system, the proteins and biomolecules in the system adsorb to the NP surface to form a “protein corona” (PC). The PC greatly influences NP transformations, biological interactions, and cell response. Further complicating the development of NPs for biomedical applications, disease states alter the population of proteins and changes the biophysical features of individual proteins through posttranslational modifications. Here-in, we aim to understand how glycation of the PC, as in uncontrolled diabetes, alters the NP-PC interaction and toxicity by conducting biochemistry and cell toxicity experiments. We focus upon 40 and 80 nm citrate-coated silver nanoparticles and glycated and unmodified human serum albumin (HSA) as a model system. To investigate the impact of glycation on NP-PC interactions, we evaluate changes to NP size and surface charge, HSA secondary structure, and binding constants for the complex. Results indicate a stable system with no particle agglomeration or protein unfolding, an increase in surface charge, and dynamic binding. To investigate the impact of the PC and glycation on NP interactions with human cells, we investigate changes in proliferation of HepG2 cells with addition of the complex. Results indicate the protein corona increases the cytotoxicity of the NPs. Results will contribute to the body of research exploring how nanoparticles change when they enter human systems. In the long term this research will assist in developing NPs for medical applications, especially in a diabetic population.

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