Document Detail


Perturbational profiling of nanomaterial biologic activity.
MedLine Citation:
PMID:  18492802     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Stanley Y Shaw; Elizabeth C Westly; Mikael J Pittet; Aravind Subramanian; Stuart L Schreiber; Ralph Weissleder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-29     Completed Date:  2008-06-16     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7387-92     Citation Subset:  IM    
Affiliation:
Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Assay
Cell Line
Cluster Analysis
Humans
Materials Testing / methods*
Mice
Mice, Inbred BALB C
Nanoparticles / chemistry,  toxicity*
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
K08HL077186/HL/NHLBI NIH HHS; N01-CO-12400/CO/NCI NIH HHS; P50CA086355/CA/NCI NIH HHS; U01HL080731/HL/NHLBI NIH HHS; U54CA119349/CA/NCI NIH HHS
Comments/Corrections

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