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.
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.
|Jones, David E; Ghandehari, Hamidreza; Facelli, Julio C (2016) A review of the applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles. Comput Methods Programs Biomed 132:93-103|
|Herd, Heather L; Bartlett, Kristopher T; Gustafson, Joshua A et al. (2015) Macrophage silica nanoparticle response is phenotypically dependent. Biomaterials 53:574-82|
|Dubey, Ramin; Kushal, Swati; Mollard, Alexis et al. (2015) Tumor targeting, trifunctional dendritic wedge. Bioconjug Chem 26:78-89|
|Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza (2015) Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue. Macromol Biosci 15:1735-43|
|Gustafson, Heather Herd; Holt-Casper, Dolly; Grainger, David W et al. (2015) Nanoparticle Uptake: The Phagocyte Problem. Nano Today 10:487-510|
|Robinson, Ryan; Gerlach, Wiebke; Ghandehari, Hamidreza (2015) Comparative effect of gold nanorods and nanocages for prostate tumor hyperthermia. J Control Release 220:245-52|
|Hubbard, Dallin; Enda, Michael; Bond, Tanner et al. (2015) Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue. Mol Pharm 12:4099-107|