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To measure how cancer cells respond when they take up nanoparticles, Dr. Mirkin and his colleagues used a technique known as genome-wide expression profiling, which measures relative changes in global gene expression. The investigators added different types of nanoparticles to cancer cells growing in culture dishes and then obtained whole genome expression profiles for the cells. In all the experiments, the researchers attached non-targeting nucleic acids attached to the nanoparticles in order to minimize gene changes that might be triggered through a therapeutic effect relating to a specific, designed interaction between the nucleic acid and a targeted gene.
The results of these comparison studies showed that the surface properties of the nanoparticles had a profound impact on how a given nanoparticle impacts gene expression within a cell. The researchers observed the most surprising and noteworthy difference when they compared two nanoparticles that differed only in the manner in which the nucleic acids were attached to the nanoparticle surface. Nanoparticles loosely linked to the nucleic acids triggered large-scale changes in gene expression, while in contrast, nanoparticles linked tightly to nucleic acids through a covalent chemical bond had virtually no effect on gene expression. These findings, the researchers noted, show how important it is to fully characterize nanoparticles not only in terms of the shape and size, but also with respect to their surface properties.
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