Perturbational profiling of nanomaterial biologic activity

Our understanding of the biologic effects (including toxicity) of nanomaterials is incomplete.In vivo animal studies remain the gold standard; however, widespread testing remains impractical, and the development ofin vitro assays that correlate within vivo activity has proven challenging. Here, we demonstrate the feasibility of analyzingin vitro nanomaterial activity in a generalizable, systematic fashion. We assessed nanoparticle effects in a multidimensional manner, using multiple cell types and multiple assays that reflect different aspects of cellular physiology. Hierarchical clustering of these data identifies nanomaterials with similar patterns of biologic activity across a broad sampling of cellular contexts, as opposed to extrapolating from results of a singlein vitro assay. We show that this approach yields robust and detailed structure–activity relationships. Furthermore, a subset of nanoparticles were tested in mice, and nanoparticles with similar activity profilesin vitro exert similar effects on monocyte numberin vivo . These data suggest a strategy of multidimensional characterization of nanomaterialsin vitro that can inform the design of novel nanomaterials and guide studies ofin vivo activity.