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Title: Novel amphiphilic core-shell nanocomposite particles for enhanced magnetic resonance imaging
Authors: Chen, Lianghui
Degree: Ph.D.
Issue Date: 2017
Abstract: Magnetic resonance imaging (MRI) is one of the most useful diagnosis toolkits because of its inherent advantages such as non-invasiveness, safety, and high spatial resolution. In most clinical applications, MRI contrast agents are used in order to increase sensitivity and quality of the MR images for accurate diagnosis. Iron oxide-based nanoparticles, commonly used as the negative MRI contrast agents, have attracted increasing research interest owing to their several key advantages such as high negative T₂ contrast property, size-tunable feature and low cytotoxicity in in vivo application. This thesis aims to develop novel and robust iron oxide-based MRI contrast agents through a novel and scalable synthetic route. Specifically, vinyl-coated γ-Fe₂O₃ nanoparticles were encapsulated into amphiphilic core-shell polymeric particles, which consist of poly(methyl methacrylate) (PMMA) cores and biocompatible chitosan (CTS) shells via a surfactant-free emulsion polymerization method. The hydrophilic chitosan shell provides surface functionality and colloidal stability for the nanocomposite particles in aqueous. The hydrophobic nano-sized PMMA core embeds multiple γ-Fe₂O₃ nanoparticles. These confined γ-Fe₂O₃ nanoparticle aggregates show much better MRI performance than those individually dispersed γ-Fe₂O₃ nanoparticles. Thus, this type of magnetic core-shell nanocomposite particles is a promising T2-weighted MRI contrast agents. The thesis begins with the introduction of the MRI technique as well as its history and basic physics principle. Current MRI contrast agents are discussed with an emphasis on the T₂-weighted MRI contrast agents. This chapter also reviews the current approaches to prepare iron oxide-based contrast agents and points out drawbacks of these methodologies. Various strategies to enhance r₂ relaxivities of the contrast agents and their disadvantages are also described. Chapter Two presents a novel type of amphiphilic core-shell nanoparticles which have been developing in Professor Pei Li's group. The particle formation mechanism and properties of this type of amphiphilic core-shell nanoparticles are highlighted. Chapter Three provides the rationale for the design and synthesis of amphiphilic core-shell nanocomposite particles as MRI contrast agents. The general and specific objectives of this research are described. Chapter Four describes the synthesis, surface modification and characterization of hydrophobic iron oxide nanoparticles. The magnetic nanoparticles were systematically characterized using various advanced analytical instruments such as dynamic light scattering (DLS) and zeta-potential measurement; Fourier Transform Infrared Spectroscopy (FTIR); thermogravimetric analysis (TGA); X-ray diffraction spectroscopy (XRD). Results show that the hydrophobic γ-Fe₂O₃ nanoparticles contain 10-20 w.t.% surface coating for subsequent polymerization and a high degree of crystallinity with minor defects.
Chapter Five discusses the synthesis and characterization of magnetic amphiphilic nanocomposite particles. The γ-Fe₂O₃@PMMA/CTS core-shell nanocomposite particles were first prepared via a surfactant-free emulsion polymerization, followed by the particle purification steps. Chemical structures of the γ-Fe₂O₃@PMMA/CTS particles were identified by the FTIR. Transmission electron microscopy (TEM) images revealed that the nanocomposite particles had a well-defined core-shell nanostructure with numerous iron oxide nanoparticles being encapsulated within the PMMA cores. XRD profile suggests that crystallinity of the encapsulated iron oxide nanoparticles was not altered after the polymerization process. The nanocomposite particles exhibited saturation magnetization (ms) of 11.6 emu/g at 298 K with the superparamagnetic property. Optimization of the synthesis is also described in this chapter. Effects of monomer and iron oxide nanoparticle dosages, types of initiator, as well as initiator concentration, were systematically examined. Results indicated that lowering MMA ratio could reduce the hydrodynamic diameter of the nanocomposite particles, and increase the encapsulation efficiency. When the weight ratio of CTS to MMA to vinyl-coated γ-Fe₂O₃ nanoparticles was 15.2 : 6.1 : 1, encapsulation content of magnetic nanoparticles of the resulting nanocomposite particles was as high as 42.4 w.t.% with an average particle size less than 400 nm in diameter. Chapter Six explores the application of magnetic core-shell nanocomposite particles as a potential MRI contrast agent. The nanocomposite particles showed long-term stability and very low cytotoxicity to L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). For MRI application, the nanocomposite particles exhibited a T₂ relaxivity of up to 364 mMFeˉ¹sˉ¹. An in vivo MRI test performed on a breast-tumor-bearing nude mouse indicated that the nanocomposite particles could localize in both normal liver and tumor tissues through the reticuloendothelial system (RES) and the enhanced permeability and retention (EPR) effect, respectively. The final chapter summarizes the key findings obtained in this thesis and provides some recommendation for a future investigation. Significance and implications made in this work are also highlighted.
Subjects: Hong Kong Polytechnic University -- Dissertations
Magnetic resonance imaging
Pages: xvii, 205 pages : color illustrations
Appears in Collections:Thesis

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