DESIGN and SYNTHESIS of MULTIFUNCTIONAL NANOPARTICLES for MULTI-MODAL IMAGING and THERANOSTICS APPLICATIONS

Li, Du

DESIGN and SYNTHESIS of MULTIFUNCTIONAL NANOPARTICLES for MULTI-MODAL IMAGING and THERANOSTICS APPLICATIONS

Li, Du

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Publication Type:: Thesis
Issue Date:: 2020

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Field	Value	Language
dc.contributor.author	Li, Du
dc.date.accessioned	2020-11-17T03:27:08Z
dc.date.available	2020-11-17T03:27:08Z
dc.date.issued	2020
dc.identifier.uri	http://hdl.handle.net/10453/144091
dc.description	University of Technology Sydney. Faculty of Science.	en_AU
dc.description.abstract	Tumor imaging can localize neoplastic lesions in the body. Since early detection of tumors will improve early treatment and prognosis, continuing to enhance current multi-modal tumor imaging approaches towards higher sensitivity, resolution, and speed is critically needed in guiding the personalized therapy. Contrast agents are often essential in significantly improving the imaging quality to achieve better limits of detection for cancer cells. Clinically used contrast agents are generally based on small molecules, which suffers from severe disadvantages such as short half-decay time and non-specificity. With the rapid development of nanotechnology, nanoscale contrast agents have been extensively synthesized and applied for early detection of tumors with prolonged residence time in the bloodstream and passive targeting abilities. Nanoparticle-based contrast agents have relatively large surface-to-volume ratios to enhance surface binding and the amount of payloads for nanomedicine delivery. Their compositions, morphology and surface properties are tunable, which renders them with unique properties compensating the drawbacks of molecular contrast agents. Nanoscale contrast agents can incorporate tumor targeting agents to promote the specific targeting abilities with improved imaging contrast and detection sensitivity. Moreover, multifunctional nanoparticles can be made with robust and well-defined surfaces to incorporate multimodal imaging, targeting biomolecules, and drug delivery as both diagnostic agents and theranostic vehicles. This thesis reports the rational design, synthesis and tumor imaging applications of various nanoscale contrast agents, including gold nanoparticles (AuNPs) for Computed Tomography (CT) imaging, gadolinium ions modified nanoparticles for Magnetic Resonance (MR) imaging, upconversion nanoparticles for optical imaging. Hyperbranched polyethyleneimine (PEI) polymeric carriers have been used as the template for the fabrication of contrast agents, which offers several advantages, including abundant terminal groups for surface modification, improved solubility and stability, biocompatibility, and prolonged circulation. Particularly, I have demonstrated the dual mode CT/MR tumor imaging abilities of Au/gadolinium and Au/Gd₂O₃ nanoparticles-based nanoparticles. Polydopamine-coated Au nanostars have been fabricated for CT imaging and enhanced photothermal therapy of tumors. Furthermore, I have demonstrated the fabrication of photon up-converting nanoparticle probes with improved brightness to realize tumor imaging using low irradiance of near infrared excitation. These findings provide new ideas and directions for the development of new multimodal imaging contrast agents and multifunctional therapeutic agents.	en_AU
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/144091/2/02whole.pdf
dc.rights	au.edu.uts.lib/ppc
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	info:eu-repo/semantics/openAccess
dc.title	DESIGN and SYNTHESIS of MULTIFUNCTIONAL NANOPARTICLES for MULTI-MODAL IMAGING and THERANOSTICS APPLICATIONS	en_AU
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Tumor imaging can localize neoplastic lesions in the body. Since early detection of tumors will improve early treatment and prognosis, continuing to enhance current multi-modal tumor imaging approaches towards higher sensitivity, resolution, and speed is critically needed in guiding the personalized therapy. Contrast agents are often essential in significantly improving the imaging quality to achieve better limits of detection for cancer cells. Clinically used contrast agents are generally based on small molecules, which suffers from severe disadvantages such as short half-decay time and non-specificity. With the rapid development of nanotechnology, nanoscale contrast agents have been extensively synthesized and applied for early detection of tumors with prolonged residence time in the bloodstream and passive targeting abilities. Nanoparticle-based contrast agents have relatively large surface-to-volume ratios to enhance surface binding and the amount of payloads for nanomedicine delivery. Their compositions, morphology and surface properties are tunable, which renders them with unique properties compensating the drawbacks of molecular contrast agents. Nanoscale contrast agents can incorporate tumor targeting agents to promote the specific targeting abilities with improved imaging contrast and detection sensitivity. Moreover, multifunctional nanoparticles can be made with robust and well-defined surfaces to incorporate multimodal imaging, targeting biomolecules, and drug delivery as both diagnostic agents and theranostic vehicles. This thesis reports the rational design, synthesis and tumor imaging applications of various nanoscale contrast agents, including gold nanoparticles (AuNPs) for Computed Tomography (CT) imaging, gadolinium ions modified nanoparticles for Magnetic Resonance (MR) imaging, upconversion nanoparticles for optical imaging. Hyperbranched polyethyleneimine (PEI) polymeric carriers have been used as the template for the fabrication of contrast agents, which offers several advantages, including abundant terminal groups for surface modification, improved solubility and stability, biocompatibility, and prolonged circulation. Particularly, I have demonstrated the dual mode CT/MR tumor imaging abilities of Au/gadolinium and Au/Gd₂O₃ nanoparticles-based nanoparticles. Polydopamine-coated Au nanostars have been fabricated for CT imaging and enhanced photothermal therapy of tumors. Furthermore, I have demonstrated the fabrication of photon up-converting nanoparticle probes with improved brightness to realize tumor imaging using low irradiance of near infrared excitation. These findings provide new ideas and directions for the development of new multimodal imaging contrast agents and multifunctional therapeutic agents.

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