Perturbational profiling of nanomaterial biologic activity.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

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 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 Publication
2008
Journal
Proc Natl Acad Sci U S A
Volume
105
Issue
21
Pages
7387-92
Date Published
2008 May 27
ISSN
1091-6490
DOI
10.1073/pnas.0802878105
PubMed ID
18492802
PubMed Central ID
PMC2396702
Links
Grant list
U01 HL080731 / HL / NHLBI NIH HHS / United States
P50 CA086355 / CA / NCI NIH HHS / United States
K08HL077186 / HL / NHLBI NIH HHS / United States
U54CA119349 / CA / NCI NIH HHS / United States
P50CA086355 / CA / NCI NIH HHS / United States
U54 CA119349 / CA / NCI NIH HHS / United States
U01HL080731 / HL / NHLBI NIH HHS / United States
K08 HL077186 / HL / NHLBI NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States