Award Date

August 2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Health Physics and Diagnostic Sciences

First Committee Member

Steen J. Madsen

Second Committee Member

Ralf Sudowe

Third Committee Member

Gary Cerefice

Fourth Committee Member

Patricia T. Alpert

Number of Pages

57

Abstract

Gold-based nanoparticles including gold-silica nano-spheres and gold nano-rods have been investigated for a number of therapeutic and diagnostic applications. The ability of these nanoparticles to convert light into heat energy makes them particularly appealing for photothermal therapy in which cancer cells are destroyed via light-induced heat generation. The overall objective of the study is to compare the efficacy of gold-silica nano-spheres and gold nano-rods in an in vitro system consisting of human brain tumor (glioma) spheroids.

Delivery of the nanoparticles to the spheroids was accomplished using murine macrophages. Nanoparticles (spheres or rods) were incubated with macrophages for 24 hours. Thereafter, nanoparticle-loaded macrophages were combined with human glioma cells and centrifuged in order to create a hybrid spheroid. Approximately 48 hours post centrifugation, the resultant 400 µm dia. spheroids were exposed to 808 nm laser light for 10 min at irradiances of 2, 7, 14 and 28 W cm-2. Treatment efficacy was evaluated from spheroid growth kinetics over a 14-day period.

Gold nanoshells were shown to have greater efficacy compared to gold nanorods. For example, hybrid spheroids consisting of a 5:1 ratio of glioma cells to nanosphere-loaded macrophages exhibited significant growth inhibition when subjected to irradiances of 7 W cm-2. In contrast, no growth inhibition was observed for the nanorod-macrophage hybrid spheroids, even at the highest irradiance investigated (28 W cm-2). Growth inhibition was observed at 28 W cm-2 when the nanorod concentration was increased, i.e., by forming hybrid spheroids with a 2:1 ratio of glioma cells to macrophages.

Gold nano-spheres are better photo-thermal agents compared to gold nanorods. The work highlights the potential of gold nano-spheres in the treatment of brain tumors using laser-induced photothermal therapy as an adjuvant to conventional therapies.

Keywords

Gold Nanorods; Gold-silica Nanoshells; Macrophage; Nanoparticles; Photothermal Thepary; Spheroids

Disciplines

Biophysics | Medicine and Health Sciences | Oncology

Language

English


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