Photoacoustic imaging using nanoclusters




Yoon, Soon Joon

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Advances in novel imaging techniques and molecular probes are now extending the opportunity of visualizing molecular targets of disease. Molecular imaging provides anatomic as well as functional and pathological information to sense the expression of molecular biological events. In general, molecular imaging aims to target a specific cell type or tissue and visualize biological events in vivo at the molecular or cellular levels through specific probes. Molecular imaging is usually performed in conjunction with probes for specific targets. The objective of this dissertation is to explore molecular imaging by providing highly efficient photoacoustic nanocluster contrast agents to further validate in vivo molecular imaging, improve the therapeutic procedure, and study fundamental photoacoustic signal processes from cluster of nanoparticles. Initially, a photothermal stimuli-responsive photoacoustic nanocluster was designed and synthesized to provide highly sensitive dynamic contrast within tissue samples. The photoacoustic signal enhancement from clustering of nanoparticles was demonstrated by characterizing the photoacoustic signal from photothermal stimuli-responsive nanoclusters. After characterization, photothermal stimuli-responsive nanoclusters were injected into a mouse tissue and the dynamic photoacoustic response from the nanoclusters activated by an external laser source was observed. This activation can be repeatedly turned on by modulating input laser signals, suggesting a new route for dynamic photoacoustic contrast imaging that will further improve the imaging contrast and more accurately guide the drug release process. Despite tremendous advantages of using these nanoparticles, their safety in a biological environment could be a major hurdle for their in vivo utilization. In order to avoid accumulation and long-term toxicity of nanoparticles, biodegradable nanoclusters consisting of sub-5 nm primary gold particles stabilized by a weakly adsorbed biodegradable polymer were introduced. The photoacoustic signal from biodegradable nanoclusters was quantitatively characterized. In addition, photothermal stability of different sizes of biodegradable nanoclusters was investigated. These nanoclusters were then intravenously injected into mice and biodistribution of nanoparticles was observed. Finally, in vivo spectroscopic photoacoustic imaging was performed on tumor-bearing mice with antibody conjugated biodegradable nanoclusters. This research may provide a new opportunity for molecular imaging to help diagnose tumors at an early stage and promote clinical translation of these techniques.


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