When mixing citrate-capped gold nanoparticles with blood plasma or serum, a layer of proteins along with other biomolecules can adsorb instantly to the nanoparticle surface to form a biomolecular corona. Because a pathological condition can change the quantity or types of proteins and other relevant biomolecules present in the blood, we hypothesize that by analyzing the composition of the biomolecular corona, it is possible to discover molecular differences between patients versus healthy controls, and such molecular differences may be used as biomarkers for diagnostic applications. We have developed a dynamic light scattering-based assay platform to detect and analyze the specific proteins adsorbed to the gold nanoparticle surface. The assay involves a simple two-step process as illustrated in Figure 1: in the first step, a few microliter of blood plasma or serum is mixed with a citrate-capped gold nanoparticle solution. After 5-15 min of incubation, a stable biomolecular corona is formed on the nanoparticle surface. The formation of the biomolecular corona will lead to an increase in the average particle size of the assay solution. Then in a second step, an antibody specific to the interested target protein in the nanoparticle corona is added to the assay solution. If a target protein is present in the corona, the binding of the antibody with the target protein in the corona will lead to nanoparticle aggregation, and such aggregate formation is readily detected by dynamic light scattering. A test score, expressed as the ratio of the average particle size measured from the second step versus the first step of the assay, reveals the relative quantity of the target protein present in the biomolecular corona. Using this platform, we were able to detect active immune response associated with acute viral infection and certain type of cancer. By varying the assay platform slightly, we developed a rapid blood test for Zika viral infection diagnosis. Our work demonstrates that the analysis of biomolecular corona formed on the nanoparticle surface in blood provides a rich opportunity for biomarker detection and diagnostic test development.<br/>

Biomolecular corona of gold nanoparticles formed in blood: Application for detection and diagnosis of infectious diseases and cancer

255th National Meeting (2018)

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