<p>The prevalence of cancer has increasingly become a significant threat to human health and as such, there exists a strong need for developing novel methods for early detection and effective therapy. Nanotheranostics, a combination of diagnostic and therapeutic functions into a single nanoplatform, has great potential to be used for cancer management by allowing detection, real-time tracking, image-guided therapy and therapeutic response monitoring. Gold nanostars (GNS) with tip-enhanced plasmonics have become one of the most promising platforms for cancer nanotheranostics. This work is aimed at addressing the challenges of sensitive cancer detection, metastasis treatment and recurrence prevention by combining state-of-the-art nanotechnology, molecular imaging and immunotherapy. A multifunctional GNS nanoprobe is developed with capabilities ranging from non-invasive, multi-modality cancer detection using positron emission tomography (PET), magnetic resonance imaging (MRI) and X-ray computed tomography (CT), to intraoperative tumor margin delineation with surface enhanced Raman spectroscopy (SERS) and high-resolution nanoprobe tracking with two-photon photoluminescence (TPL), as well as cancer treatment with photoimmunotherapy. The GNS nanoprobe with PET scans is particularly exceptional in detecting brain malignancies as small as 0.5 mm. To the best of our knowledge, the developed GNS nanoprobe for PET imaging provides the most sensitive means of brain tumor detection reported so far. In addition, the GNS nanoprobe exhibits superior performance as photon-to-heat transducer and can be used for specific photothermal therapy (PTT). More importantly, GNS-mediated PTT combined with checkpoint inhibitor immunotherapy has been found to trigger a memorized immunoresponse to treat cancer metastasis and prevent recurrence in mouse model studies. Furthermore, a 6-month in vivo toxicity study including body weight monitoring, blood chemistry test and histopathology examination demonstrate GNS nanoparticles’ biocompatibility. Therefore, the multifunctional GNS nanoprobe exhibits superior cancer detection and treatment capabilities and has great promise for future clinical translation in cancer management.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/13391 |
| Date | January 2016 |
| Creators | Liu, Yang |
| Contributors | Vo-Dinh, Tuan |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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