Scientific Publications

Perturbational profiling of nanomaterial biologic activity.

Publication TypeJournal Article
AuthorsShaw, SY, Westly EC, Pittet MJ, Subramanian A., Schreiber SL, and Weissleder R.
AbstractOur 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 of in vitro assays that correlate with in vivo activity has proven challenging. Here, we demonstrate the feasibility of analyzing in 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 single in 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 profiles in vitro exert similar effects on monocyte number in vivo. These data suggest a strategy of multidimensional characterization of nanomaterials in vitro that can inform the design of novel nanomaterials and guide studies of in vivo activity.
Year of Publication2008
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue21
Pages7387-92
Date Published (YYYY/MM/DD)2008/05/27
ISSN Number0027-8424
DOI10.1073/pnas.0802878105
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/18492802?dopt=Abstract