Electronic Theses and Dissertations

Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

Committee Chair

Xiaohua Huang

Committee Member

Yongmei Wang

Committee Member

Gary Emmert

Committee Member

Abby Parrill

Abstract

Gold and hybrid gold nanotechnology are uniquely poised to improve the fields of cancer diagnosis and therapy. Modifying gold nanoparticles with biological proteins has been widely used for decades, however, the common carbodiimide technique requires steps that reduce sensitivity and effectiveness in some spectroscopic techniques. We have developed an antibody conjugation protocol which conducts linking first, and then covalently adheres the antibody-linker complex to the nanoparticle surface. The linking polymer N-hydroxysuccinimide-polyethylene glycol-thiol (NHS-PEG-SH) was incubated with a protein overnight and purified by centrifuge filtration before modifying the surface of gold nanoparticles by slow mixing. The method was transferred to antibody conjugation and cell-labeling strength and specificity verified via dark field imaging of cell lines with known expressions. In cancer treatment, nanoparticles have been implemented in promising phototherapeutic strategies. Here, we describe the development of a nanocomplex which augments photothermal therapy via gold nanorods with the addition of a photosensitizer for dual photothermal-photodynamic (PTT/PDT) therapy under a single laser irradiation. Silicon 2,3-napthallocyanine dihydroxide (SiNC) was adsorbed onto gold nanorods and stabilized with alkylthiol-polyethylene glycol. Cytotoxicity was analyzed in vitro under laser treatment. It was found that the nanocomplex produced cell-killing effects with efficiency greater than PTT or PDT alone under low dosage and cell-killing efficiency increased with increasing alkylthiol length. This nanocomplex has potential to non-invasively destroy tumor cells in a localized area, preventing tumor resurgence. In cancer detection, circulating tumor cells (CTCs) are the hallmark of metastasis and an ideal target for liquid biopsies but are exceptionally rare. Here we develop on the previous system by using multiplexed antibody-targeted SERS-active iron oxide-gold core-shell nanopopcorn in conjunction with a miniaturized chip to capture CTCs from whole blood and analyze individual cells to construct a molecular profile of common cancer markers. We demonstrate the capability of the nanoparticles to selectively capture and profile cancer cells individually and with multiplexed labeling with an integrated microfluidic device. Labeled cancer cells spiked into PBS are swiftly captured with high efficiency, and detected nanoparticle ratios agree with cell line expressions. This method provides a rapid integrated method for CTC capture, detection, and profiling of surface markers.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

embargoed

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