Monitoring nanoparticle aggregation in complex biological environments

by Jenkins, Samir V.; Zhang, Yongbin; Chen, Jingyi

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Gold nanoparticles (NPs) are a promising candidate for a theranostic platform. They are typically administered i.v. and, therefore, immediately encounter blood-an extremely complex, viscous fluid with many active components. These components may cause aggregation or dissoln. of the particles, thus changing their properties. Most commonly-used characterization methods have limited capabilities for monitoring the status of NPs in situ following their introduction to the blood. In this study, a new methodol. is developed to reveal the changes of NPs in complex biol. solns. (e.g. blood) using reflectance hyperspectral imaging coupled with Raman spectroscopy. The aggregation of the NPs is monitored based on the changes of the optical resonance of the particles by hyperspectral imaging. These results are further correlated with the Raman enhancement of the protein adsorbed on the NPs. Using this method, the fate of the citrate-capped gold NPs in the blood is examd. and compared with that of the silver NPs. Little aggregation is obsd. after 18 h incubation of gold NPs in ex vivo rat blood, while the silver NPs showed a greater tendency toward aggregation in the blood. Addnl., the fate of NPs following macrophage uptake is examd. Some particle aggregation is obsd. following uptake and sequestration in endosomes of macrophages, but the NPs generally remained unaggregated despite the short interparticle distance within the cell.