Abstract
Nanoparticles are finding utility in myriad biotechnological applications, including gene regulation, intracellular imaging, and medical diagnostics. Thus, evaluating the biocompatibility of these nanomaterials is imperative. Here we use genome-wide expression profiling to study the biological response of HeLa cells to gold nanoparticles functionalized with nucleic acids. Our study finds that the biological response to gold nanoparticles stabilized by weakly bound surface ligands is significant (cells recognize and react to the presence of the particles), yet when these same nanoparticles are stably functionalized with covalently attached nucleic acids, the cell shows no measurable response. This finding is important for researchers studying and using nanomaterials in biological settings, as it demonstrates how slight changes in surface chemistry and particle stability can lead to significant differences in cellular responses.