Engineered nanomaterial's have unique electrical, mechanical and physicochemical properties with potential to impact many facets of our society. However, the health and safety of nanomaterial's has recently become a major concern to the public as well as to policy makers and funding agencies. Such concern is justified in light of the vast potential for nanomaterial use in food, cosmetics, medicine, construction, bioimaging, as well as the potential exposures during manufacturing or research use. It has recently been established that nanomaterials, upon entry into a physiological environment, exhibit a tendency of physical adsorption with proteins, peptides, lipids and amino acids to render a protein "corona" that may influence the bioavailability and distribution of nanomaterials within the host system, at the cellular, tissue and whole organism level. Consequently, research on the health and safety implications of nanomaterials must address the following two key questions: 1) protein binding kinetics and conformational change resulting from their interaction with the nanoparticle, 2) recognition of protein corona by cellular receptors and subsequent immune responses to both the nanomaterial and the altered protein structure. The central hypothesis of this project is that the physicochemical interactions between nanomaterials and the "corona" components leads to changes in protein conformation, which will subsequently result in macrophage and dendritic cell activation and differential antigen presentation. We will test this hypothesis by: 1) characterizing a set of nanoparticle protein coronas;2) determining the in vitro cellular and immune fate of nanoparticle protein corona. Understanding the impact of nanomaterial protein corona on immune response will be crucial for the development of safe nanotechnologies.

Public Health Relevance

The unique properties that make nanomaterial a focus of science, technology and medicine also present health and safety concerns. Accordingly, this project seeks to elucidate the key physicochemical properties and processes of biomolecules interacting with nanomaterials to ultimately form a corona of proteins, lipids, fatty acids, and amino acids. More importantly, this project seeks to determine the health impact of nanomaterial corona on immune responses and antigen presentation. A cross-disciplinary approach to address the health and safety impact of nanoparticle protein corona will provide a unique study of nanomaterial that spans across biophysics, immunology and toxicology, and is in line with the mission of the NIEHS.

Agency
National Institute of Health (NIH)
Type
Small Research Grants (R03)
Project #
1R03ES023036-01A1
Application #
8769110
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Nadadur, Srikanth
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Aurora
State
CO
Country
United States
Zip Code
80045