The use of nanoparticles in biomedical applications has greatly increased in recent years due to their unique properties, which allow them to supplement or even surpass the effectiveness of traditional treatments. Multiple types of nanoparticles are currently utilized or proposed for use in medicine, including gold, silver, and iron oxide. Each of these substances confer a unique set of benefits; gold has anti-inflammatory properties, silver is antibacterial, and iron oxide, in addition to being relatively inert, is useful is treating those with anemia. Unfortunately, many of the properties which make nanoparticles potentially useful for medical applications frequently contribute to their toxicity. While studies have been performed which examine the toxicity of nanoparticle therapeutics, virtually all have taken place in healthy conditions. This is not representative of the conditions in which these nanoparticles will be used, as treatments are, by definition, given to individuals who are somehow unhealthy. Additionally, a large and growing proportion of the population in the United States and worldwide suffer from a chronic disease, with some of the most common being obesity, high cholesterol, and metabolic syndrome. It is therefore important to consider these individuals in the development and testing of nanoparticle therapeutics. Specifically, these diseases alter the content of the circulation beyond the differences which exist solely due to individual variability. This may in turn may alter the biocorona, the term given to the coating of biomolecules which forms on the nanoparticle surface following exposure to a physiological environment. We hypothesized that individual variability and disease, specifically the common diseases obesity, high cholesterol, and metabolic syndrome, would alter the content of the biocorona, and that this would translate to differential nanoparticle toxicity.It was determined that both disease and individual variability caused distinct alterations in the biomolecular content of the biocorona. Further, these alterations were found to elicit distinct inflammatory responses when comparing between individuals or healthy to diseased conditions. These results have implications for the use of nanoparticles in biomedicine, as the variability observed within the biocoronain disease and between individuals may have a significant impact on the efficacy of the treatment,as well as any toxicological effects. It is therefore in the interest of public health to modify the process of developing, testing, and utilizing nanoparticle therapeutics such that the biocorona may work in conjunction with or regardless of differences in the biological milieu which exist as a result of individual variability or disease. By this, researchers 18ABSTRACTThe use of nanoparticles in biomedical applicationshas greatly increased in recent years due to their unique properties, which allow them to supplement or even surpass the effectiveness of traditional treatments. Multiple types of nanoparticles are currently utilized or proposed for use in medicine, including gold, silver, and iron oxide. Each of these substances confer a unique set of benefits; gold has anti-inflammatory properties, silver is antibacterial, and iron oxide, in addition to being relatively inert, is useful is treating those with anemia. Unfortunately, many of the properties which make nanoparticles potentially useful for medical applications frequently contribute to their toxicity. While studies have been performed which examine the toxicity of nanoparticle therapeutics, virtually all have taken place in healthy conditions. This is not representative of the conditions in which these nanoparticles will be used, as treatments are, by definition, given to individuals who are somehow unhealthy. Additionally, a large and growing proportion of the population in the United States and worldwide suffer from achronic disease, with some of the most common being obesity, high cholesterol, and metabolic syndrome. It is therefore important to consider these individuals in the development and testing of nanoparticletherapeutics. Specifically, these diseases alter the content of the circulationbeyond the differences which exist solely due to individual variability. This mayin turn may alter the biocorona, the term given to the coating of biomolecules whichforms on the nanoparticle surface following exposure toa physiologicalenvironment. We hypothesized that individual variability and disease, specifically the common diseases obesity, high cholesterol, and metabolic syndrome, would alter the content of the biocorona, and that this would translateto differential nanoparticle toxicity.It was determined that both disease and individual variability caused distinct alterations in the biomolecular content of the biocorona. Further, these alterations were foundto elicit distinct inflammatory responses when comparing between individuals or healthy to diseased conditions. These results have implications for the use of nanoparticles in biomedicine, as the variability observed within the biocoronain disease and between individuals may have a significant impact on the efficacy of the treatment,as well as any toxicological effects. It is therefore in the interest of public health to modify the process of developing, testing, and utilizing nanoparticle therapeutics such that the biocorona may work in conjunction with or regardless of differences in the biological milieu which exist as a result of individual variability or disease. By this, researchers.