The global goal of this project is to assess how physicochemical characteristics of nanomaterials modulate biological environmental responses. In this application the influence of porosity, degradation and curvature of silica nanoparticles (SNPs) on mechanisms of cellular uptake, biodistribution, pharmacokinetics and toxicity will be examined. Specifically, we will examine in more detail the cellular fate and mechanisms of intracellular transport of the SNPs, how inflammatory responses are initiated in response to the changes in the physicochemical properties, and what would be the biological fate of degradation products of SNPs.
Three Specific Aims are proposed: 1) 1. Synthesis and characterization of SNPs with systematic differences in size, porosity, surface roughness and functionality, and biodegradability, 2) Investigate how surface properties affect protein and cellular inflammatory mediated mechanisms in vitro, 3) Investigate chronic inflammatory mediated mechanisms as a function of surface properties in vivo.

Public Health Relevance

Nanomaterials are increasingly used in biomedical applications. A detailed understanding of potential mechanisms of toxicity of such materials as a function of their structure will provide guidelines for development of safe engineered structures.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
9R01ES024681-06A1
Application #
8761265
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Nadadur, Srikanth
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Hubbard, Dallin; Enda, Michael; Bond, Tanner et al. (2015) Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue. Mol Pharm 12:4099-107