Engineering of Multifunctional Nanomaterials for Cancer Theranostics
Author | : Shreya Goel |
Publisher | : |
Total Pages | : 190 |
Release | : 2017 |
Genre | : |
ISBN | : |
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Development of novel imaging probes for cancer diagnosis is critical for early disease detection and management. The past two decades have witnessed a surge in the development and evolution of radiolabeled nanoparticles as a new frontier in personalized cancer nanomedicine. The dynamic synergism of positron emission tomography (PET) and nanotechnology combines the sensitivity and quantitative nature of PET with the multifunctionality and tunability of nanomaterials, which can help overcome certain key challenges in the field. Silica, "generally recognized as safe" (GRAS) by the Food and Drug Administration (FDA) of the United States, has emerged as one of the leading nanomaterials employed for molecular imaging and therapy of a wide variety of diseases, including cancer. However in vivo biodistribution and active targeting of silica-based nanomaterials has remained a relatively under explored area, based mainly on semi-quantitative techniques such as fluorescence imaging. In this dissertation, I explore the concept of radiolabeled silica nanoparticles for vasculature-targeted imaging of different tumor types. Both chelator-based and chelator-free radiolabeling techniques were employed for accurate and quantitative analysis of the in vivo pharmacokinetics of radiolabeled silica nanomaterials. (Chapters 2 and 3) The large surface area, ease of tunability and facile silica chemistry were employed to create multifunctional silica-based materials to simultaneously seek-and-treat cancers, by incorporating multiple components into a single nanoplatform. Photodynamic agent, porphyrin was loaded into the central cavity of hollow mesoporous silica nanoparticles, and the shell was decorated with photothermal nanoparticles, CuS, yielding a multimodal theranostic nanoplatform which could synergistically annihilate the tumor without relapse. (Chapter 4) A major hurdle in the successful clinical translation of nanomaterials is their rapid sequestration by the organs of the reticuloendothelial system (RES), mainly liver and spleen, and prolonged retention in the body, raising long-term toxicity concerns. To combat this issue, two approaches were employed; (i) Synthesis of biodegradable mesoporous silica nanoparticles (Chapter 5), and (ii) development of ultrasmall nanoparticles including renal clearable Au nanoparticles and hepatically cleared ultrasmall mesoporous silica nanoparticles (Chapter 6); for prolonged blood circulation, enhanced tumor uptake and rapid clearance from the body, enabling unprecedented tumor-to-normal tissue contrast. Overall, the reported studies explore the synergism of molecular imaging and therapy, and nanotechnology. While the application of nanomaterials in the former imparts multifunctionality to the molecular agent, allowing multimodal imaging and synergistic therapeutic regimes to be carried out simultaneously; molecular imaging techniques such as PET, allow accurate measurement of the in vivo pharmacokinetics of the nanomaterials, playing a major role towards their successful clinical translation. Further work will be required to better understand the in vivo biodistribution of both biodegradable and ultrasmall nanomaterials, and further employ them for early and specific detection of cancer, effective treatment and monitoring.