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Access Type

WSU Access

Date of Award

January 2016

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

Arun K. Iyer

Abstract

The bleak prognosis for patients diagnosed with metastatic cancer along with the low therapeutic efficacy and the recurrence of cancer in conventional chemotherapy are prompting clinical medicine to adopt a new strategy to detect cancer in early stage and to deliver the anticancer drugs specifically to tumor site to enhance therapeutic efficiency and minimize side effects. The aim of this study is to design a theranostic nanocarrier consisting of iron oxide nanoparticles (SPIONs) for magnetic resonance imaging (MRI) and Polyamidoamine dendrimers conjugated with folic acid (FA-PAMAM) for active targeted delivery of a highly potent but extremely lipophilic anticancer compound 3,4-difluorobenzylidene diferuloylmethane (CDF). The resulting targeted nanoparticles SPIONs@FA-PAMAM-CDF showed a significantly enhanced MR contrast as compared to the non-targeted nanoparticles. When tested on SKOV3 (ovarian cancer cells) and HeLa (cervical cancer cells), the targeted nanoformulations showed a higher accumulation in cancer cells with a better anticancer activity, a larger population of apoptotic cells and the ability to upregulate tumor suppressor phosphatase and tensin homolog (PTEN) and inhibit nuclear factor kappa B (NF-κB) which further confirmed the ability of the folate decorated nanoparticles for targeted MRI and anticancer drug delivery.

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