Date of Graduation

8-2017

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor

Gisela F. Erf

Committee Member

Charles F. Rosenkrans

Second Committee Member

Timothy J. Muldoon

Abstract

To be used in health care, the safety and effectiveness of nanoparticles needs to be tested in a living organism. The objective of this project was to develop the chicken as a convenient animal model to examine tissue targeting of intravenously (i.v.)-injected iron oxide (IO) nanoparticles. In Experiment 1, different doses of IO-COOH were i.v. injected into chickens; blood was collected at 0, 5, 15, 30, and 60 minutes post-injection; liver, spleen, lung, and kidney were collected after the last blood collection. For Experiment 2, IO-COOH and IO-PEG were i.v. injected into chickens; blood and the organs were collected at 0, 5, 15, 30, and 60 minutes postinjection. For both Experiments, IO concentration in blood was examined by iron test kit and fixed tissue sections were stained with H/E and Prussian blue stain. Portions of organs from Experiment 2 were frozen and used for preparation of homogenates and tissue-sections for immunohistochemical and/or iron-staining. For Experiment 3, the dermis of growing feathers (GF) was injected with mouse-IgG antigen (Ag); 6 hours later, IO-Ab (IO-COOH conjugated with chicken-antibody specific for mouse IgG), IO-COOH, or IO-PEG were i.v. injected into the chickens; one Ag-injected GF and one uninjected GF per chicken was collected at 0, 0.1, 0.5, 1, 2, 24, and 48 hours post-i.v.-injection; organs were collected at three and seven days post-i.v.- injection; and tissue sections of GFs and organs were stained with Prussian blue stain. Together, results of Experiment 1 and Experiment 2 revealed that IO-nanoparticles were taken up quickly by macrophages in liver and spleen, whereby IO-PEG was taken up at lower levels and slower pace by phagocytic cells when compared to IO-COOH. Experiment 3 was not successful in demonstrating delivery of intravenously injected IO nanoparticles to antigen-injected GFs. This may be due to the low dose of nanoparticles injected as well as the antigen-antibody system used. This is the first report describing organ-distribution and uptake of i.v. injected IO nanoparticles in the chicken system, setting the stage for using the avian model to test in vivo targeting effectiveness of nanoparticles.

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