Of Coo Mri Contrast Agent And The Hollow Of Sio <sub> 2 </ Sub> Microspheres Ultrasound Contrast Agents For Preparation And Application Of Research

Molecular imaging is a non-invasive, repeatable, real-time, dynamic technology that can provide visualizate the information of molecular or genetic and quantitative investigation. It is a new interdisciplinary field including molecular biology, chemistry, biochemistry and pharmacy. There are four important molecular imaging technology such as nuclear medicine imaging (NMI), optic imaging (OI), magnetic resonance imaging (MRI) and ultrasound imaging (US). Among of these techonologies, the quanlity of MRI show high spatial resolution and multiple sequence, and the US also have the advantages of real-time, cost effectiveness, portability and widely available. Recent years, a lot of advancement has been made for the contrast agents of MRI and US. In this thesis, we investigated the synthesis of water solubility CoO nanocrystals and the application for MRI, and explored the synthesis and the application of the funcational silica microspheres in US. The contents of this thesis include three chapters as shown in the following:Chapter 1, we systematically reviwed the principle and the major categories of molecular imaging and introduced the basic principle of MRI and US imaging. And then, the plan of this thesis was proposed.Chapter 2, the synthesis of hydrophilic CoO nanocrystals and application for MRI were investigated. Firstly, the hydrophobic CoO nanocrystals were synthesized by thermal decomposition of the cobalt-oleate complex. For biological applications, water-soluble CoO NCs were obtained via a facile phase-transfer method by employing amphiphilic surfactants, such as anionic (sodium dodecyl sulfate, SDS), neutral (Pluronic F127, PF127) and cationic (cetyltrimethyl ammonium bromide, CTAB). Field-dependent magnetization measurements indicated that CoO NCs were ferromagnetic and the type of surfactants around the CoO NCs played a crucial role in their magnetic properties. Characterization of MRI showed that different experimental conditions (different stabilizer, reaction time) had influence on T₂ relaxation rate. And then, the CoO NCs functionalized with PF127 (FOA@CoO) were chosen for further biologica application. Methyl thiazolyl tetrazolium (MTT) assays showed that they had low cytotoxicity in living cells. The results of cell uptake experiment indicated that obvious decrease of the transverse relaxation time T2 after internalization of living cells. Therefore, the PF127 functionalized CoO NCs shown the potential as a novel T2 contrast agents.Chapter 3, the synthesis of hollow silica microspheres and their application for ultrasound imaging were investigated. Firstly, the mono-disperse amino (–NH₂) functionalized core/shell PS@ SiO₂ microsheres were synthesized by using the positive charged polystyrene (PS) microsphere as template, via ammonia catalysis, co-hydrolysis and condensation of TEOS and APTES, and then the PS templates were selectively dissolved in THF solution to form the functional hollow silica microspheres(HSS-NH2). In the silica coating process, many experimental parameters such as the amount of ammonia catalyst, TEOS, and APS and also the addition method of APS can affect the morphology and thickness of the silica shells. The effect of each parameter on the growth of silica shells were systematically explored. And then we used the NH2 on HSS-NH2 for further coupling HSS with methoxy polyethylene glycol propionic acid (mPEG-COOH) and Rhodamine B Isothiocyanate (RBITC) to synthesized PEG-HSS and PEG-HSS-RB. Cytotoxicity test, hemolysis assay, and confocal fluorescent imaging had proved that the PEG-HSS had low cytotoxicity, good blood compatibility and cell permeability. Further in vitro ultrasound imaging of as-prepared PEG-HSS in both physiological saline solution and human blood were investigated under different imaging conditions, including different ultrasound frequencies, mechanical indexes (MIs), and different PEG-HSS concentrations, which demonstrated obvious signal enhancement. In vivo ultrasound imaging was obtained on male rat after intra-testicle injection of the PEG-HSS. These results indicated that the PEG-HSS had great potential application as a novel ultrasound contrast agent.