| Gadolinium-based T1contrast agents (CA) can improve the contrst andsensitivity of magnetic resonance imaging (MRI) diagnosis clearly and are widelyused in the scientific research and practical clinical applications. The relaxivity, as oneof the important characteristics, the level of that determines the contrast effect directly,also the stability and biocompatibility must be considered, which drives the researchto find more efficient Gd-based agents. For this reason, ultra-small gadolinium oxide(Gd2O3) nanoparticles have gained attention, due to the highest Gd density of allparamagnetic contrast agents. But they are not perfect, poor biocompatibility, highside effects, non-specific targeting limit their applications. With the goal of highrelaxivity and contrast effect, we study the preparation technique and chemicalmodification of ultra-small Gd2O3nanoparticles, and explore its application in thearea of biomedical imaging. Based on the idea that the dopa structure hasstrong adhesive force towards the metal ions, the dopamine with a catechol structurewas used to modify ultra-small Gd2O3nanoparticles. With the introduction ofdopamine, these dopamine-modified Gd2O3nanoparticles present goodbiocompatibility with the reduced toxicity, and could be used as functional imagingagents to improve the targeting selectivity or as MRI imaging probe.The innovations of this thesis were depicted as followed.(1)For the first time,the ultra-small Gd2O3nanoparticles was chemically modified by dopamine. Bydiscussing and analyzing the various factors of relaxation properties, the process ofcontrollable surface modification was expolred, to ensure the contrast enhance. Thecontrolled modification system between inorganic nanoparticles and organiccompound was built, the characterization of organic/inorganic hybrid interface wasstudie to analyze the mechanism and interaction of interface, with the boostof chemical modification for nanoparticles.(2) The relaxation rate and analysis ofT1-weighted MRI of the two kinds of Gd2O3nanoparticles was completed. Explorehow to control the density of the dopamine to the remain the enhancement effect,which has guiding significance for efficient functional contrast agents.Firstly, by optimizing the synthesis process, ultra-small gadolinium oxide (Gd2O3)nanoparticles with fine and narrow distribution of crystalline Gd2O3cores (<5nm)were prepared by the polyol method, in which, diethylene glycol (DEG) with high boiling point and dielectric constant was used as surface ligand and solution. Theweight percentage of DEG was28.8%,which could prevent the agglomeration andcontribute to disperse in water. With its high surface density of gadolinium,ultra-smallGd2O3nanoparticles show high relaxivity and better contrast enhancement effect inlow concentration, signal intensity improved with the increased concentration.The dopamine-modified Gd2O3nanoparticles was prepared based on the idea thedopamine has strong bidentate chelating ability and adhesion to metal ions. Thedensity of dopamine layer was controlled by regulating the reaction time, the molarratio and the concentration of substance, to obtain the improved stability andbiocompatibility without decreasing the contrast effect. With the weight percentageincreased, the dopamine-modified Gd2O3nanoparticles tended to aggregate because ofthe hydrophobic benzene ring in dopamine,but the introduced amino and benzene ringgroup has potential application as liver targeted agent. They effectively enhanced thecontrast brightness, and the relaxation rates and signal intensity were positivelycorrelated with the concentration of the contrast agent, although relaxivity decreasedslightly.Such research achievements not only disclosed the surface modification ofultra-small Gd2O3nanoparticles with dopamine, the relationship between relaxationrate and modification density, but also put forward new approaches and scientificviewpoints to the application and developments of novel contrast agent with improvedselective targeting or as molecular imaging probes. |
PDF Full Text Request