Detection of nanoparticle aggregation in complex, biological environments

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

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Plasmonic metal nanomaterials are promising candidates for future theranostic platforms that are in various stages of translation from the benchtop to clin. use. They are typically administered i.v. and, therefore, immediately encounter blood-an extremely complex fluid with many active components. These components may cause aggregation or dissoln. of the particles, thus changing their properties. Detg. a material's response to blood is crucial, particularly from a regulatory standpoint, to the development of new, clin. available materials. 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 spherical Au and Ag nanoparticles 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, and little aggregation was obsd. for either sample. Some particle aggregation is obsd. following uptake and sequestration in endosomes of macrophages, but the NPs generally remained nonaggregated. The methodol. is adaptable to a wide range of materials of varying shapes, compns., and functions.