Kamilla NørregaardKamilla Nørregaard

A thesis submitted March 6, 2015 for the degree of Doctor of Philosophy and defended May 18, 2015.

The PhD School of Science
Faculty of Science
Niels Bohr Institute, Optical Tweezers, University of Copenhagen

Academic advisor:
Lene Broeng Oddershede

Academic co-advisors:
Pól Martin Bendix
Andreas Kjær

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Abstract

Physics based investigations of DNA supercoiling & of plasmonic nanoparticles for photothermal cancer therapy

Hyperthermia has great potential as a cancer therapy as it weakens or causes irreversible damage to cancer cells. However, available heat sources are poor in discriminating between healthy and cancerous tissue. In this thesis work, the application of plasmonic nanoparticles as photo-induced strong, localized thermal transducers was investigated for cancer therapy.

Gold nanoparticles exhibit surface plasmon resonance that greatly enhances their photoabsorption properties. When irradiated with resonant light, they eciently absorb the light and convert it into extremely local and well-controlled heating with temperature increases that easily exceed 100. Due to these unique optical properties and their biocompatibility, gold nanoparticles are promising candidates for selective photothermal cancer therapy. Light with wavelengths in the near-infrared (NIR) region has low absorption and high penetration through biological material. Hence, the combination of these two non-destructive moieties can inict irreversible damage to the tumor tissue by strong localized hyperthermia, without harming the surrounding healthy tissue. However in the literature, the optimal choice of plasmonic nanoparticles for this therapy remains an open question.

Using positron emission tomography/computed tomography (PET/CT) imaging as a treatment evaluation tool it was found that NIR irradiated resonant silica-gold nanoshells had a higher therapeutic ecacy than non-resonant colloidal gold nanoparticles, when delivered directly into subcutaneous tumor xenografts in mice. To better understand the photo-physical properties, the plasmonic heating of the resonant and non-resonant nanoparticles was also compared using an in vitro temperature sensitive assay. This assay enabled measurements of the heat generation of single NIR irradiated nanoparticles and con rmed that the resonant silica-gold nanoshells were superior to the non-resonant nanoparticles. These ndings were in agreement with numerical photo-absorption calculations. The presented comparative study is a novel strategy to quantify the photothermal e
ect at a single particle level as well as in a therapeutic context. It is proposed that this strategy can be used to evaluate any type of nanostructure as well as di
erent tumor models.

The thesis work also contains a study of the epigenetic switch in the model system of Bacteriophage A novel assay for single particle analysis on naturally supercoiled DNA was developed, and used to investigate the effect of supercoiling on a regulatory protein-mediated DNA loop that is the basis of the epigenetic  switch. It was found that supercoiling greatly enhanced DNA looping probability, thus rendering the transition between epigenetic states an ecient and robust process. This part of the thesis project is described in three published papers that are included in this dissertation.

This thesis is not public, but if you want to read it, you can contact Kamilla Nørregaard kamilla@nbi.dk

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