Date of Completion

Spring 6-18-2018

Thesis Advisor(s)

Henry Smilowitz

Honors Major

Biomedical Engineering

Disciplines

Animal Structures | Biochemical and Biomolecular Engineering | Biomaterials | Biomechanics and Biotransport | Biomedical and Dental Materials | Inorganic Chemicals | Macromolecular Substances | Molecular, Cellular, and Tissue Engineering | Nanomedicine | Nanoscience and Nanotechnology | Nervous System | Other Biomedical Engineering and Bioengineering | Therapeutics

Abstract

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the increased radiation absorption of the INPs and subsequent increased electron and photon scattering to increase the therapeutic effect and possibly help reduce the radiation dose administered. This study serves to qualitatively and semi-quantitatively determine the distribution of the novel INPs within the murine brain, the tumor region, and at the cellular level within the tumor. This is accomplished through immunofluorescence staining and light and confocal microscopy, probing for CD31 (PECAM1), an endothelial cell marker, poly(ethylene glycol) (PEG), a nanoparticle marker, DAPI, a nucleus marker, and tdTomato, a fluorescent protein expressed by the implanted U-1242MG cells. The imaging at 10X and 63X magnification yielded evidence that the PEGylated INPs are distributed in and around the tumor to a much greater extent than elsewhere in the brain and there is some propensity for the INPs to localize in the vasculature far from the tumor region as well as within the tumor region. At the cellular level the INPs are not regularly taken up by cells and introduced into the cytoplasm within 24 hours of the last injection. Therefore, this study is relevant to radiation therapy in that it further characterizes the behavior of INPs in glioma containing murine brains, and from the data on where these particles exist, researchers can eventually develop a correlation of therapy results with INP localization at the cellular level to better develop patient treatments.

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