| Magnetic resonance imaging (MRI) is a powerful medical diagnostic technique that can differentiate normal tissue from diseased tissue and lesions in a noninvasive manner and in real-time. An MR image is generated from the nuclear magnetic resonance (NMR) of water protons. The MRI signal intensity (SI) essentially depends on the water proton density, longitudinal relaxation time (T1), and transverse relaxation time (T2) of these protons (SI∝T2or l/T1).Due to normal tissues and lesions only exhibiting small differences in relaxation time, approximately35%of all clinical MRI scans are performed with the aid of imaging contrast agents to enhance image contrast in target tissues. For clinical applications, T1contrast agents are strongly preferred over the T2agents for accurate high-resolution imaging. Because Gd3+has seven unpaired electrons with a large magnetic moment, most T1contrast agents are Gd3+-based agents. Among these agents, Gd3+complexes have been the most widely used. However, the complexes generally have a short circulating time due to rapid excretion in the urine. The complexes also provide very low local contrast, as each chelate has only one Gd3+ion, requiring large doses for effective contrast. With increasing demand on contrast agent-enhanced MRI, more and more attention has been attracted in the field of increasing local contrast and relaxivity. However, developing a T1contrast agent that exhibits further improvement in r1for ultrasensitive imaging and early diagnosis of diseases is still challenging.In addition, superparamagnetic iron oxide nanoparticle (SPIO) based biosensors, also known as magnetic relaxation switches (MRSw), have been developing fast in recent years. The assay is an important application of MRI technique. A distinct advantage of this assay is the capability to work in complex media, derived from its intrinsic magnetic properties, which may eliminate time-consuming and complex processing steps associated with conventional optical measurements. As a result, a variety of biosensors that based on MRSw technique has been designed to identify and quantify a wide variety of target analytes.Chapter1of this dissertation will briefly introduce the principles, advantages, and applications of MRI. Then we will pay a good attention on the concept, principles and classification of MRI contrast agents. After that, the recent progress in the contrast agent field will be described, with an emphasis on the T1contrast agents. Moreover, we will introduce the principle and application of SPIO-based biosensors.In chapter2, we report a novel synthesis of a poly(acrylic acid)-coated, ultra-small paramagnetic gadolinium hydrated carbonate nanoparticle (termed GHC-1). The nanoparticle is small in size and highly hydrophilic. Importantly, GHC-1exhibits a large longitudinal relaxivity at0.55T while maintaining an r2/r1ratio as low as1.17, making it effective as a T1contrast agent. Moreover, to evaluate the feasibility of GHC-1for biomedical applications, the toxicity of the nanoparticles was carefully examined in cells and animal models and the biodistribution and pharmacokinetics were monitored by in vivo MRI and in vitro elemental analysis.In chapter3, Gd3+-functionalized gold nanoclusters (Gd-AuNC) were synthesized for dual model (fluorescence/magnetic resonance) imaging. An originally designed cyclodecapeptide was employed as the template for the synthesis. The Gd-AuNC probes emit an intense red fluorescence under UV light, while exhibiting a high longitudinal relaxivity. The versatility of the probes for dual model imaging has been demonstrated by means of cellular imaging and in vivo T1-weighted MRI. Thanks to the optimal size of the nanocluster, it can freely circulate in the blood pool without significant accumulation in the liver and spleen, but with a long circulation half-life. Moreover, the nanoclusters can be noticeably excreted from the body within a period of24h through renal clearance, making it attractive for in vivo multimodal imaging.Chapter4describes an interesting observation that single-stranded oligonucleotide (ssDNA) can adsorb efficiently on carboxylic acid-functionalized magnetic nanoparticles (CAMNPs) and stabilize the nanoparticles against aggregation in weakly acidic solution. On the basis of this observation, we have designed a highly sensitive, non-sandwich type magnetic relaxation-based detection system for quantitatively probing mercury ion. By varying the concentration of CAMNPs, four orders of dynamic response range and a detection limit of0.3nM for Hg2+were achieved. Moreover, we developed a multi-sample assay to detect Hg2+in real environmental samples with high sensitivity, selectivity and efficiency.After that, in chapter5we further found that nucleotide can also adsorb efficiently on negatively charged CAMNPs. The adsorbed nucleotide can stabilize the nanoparticles well in solution, preventing the strong attraction between particles from causing them to aggregate. Inspired by this observation, we developed a magnetic relaxation-based enzyme assay for quantitative analysis of alkaline phosphatase. A detection limit of0.002unit/μL for calf intestine alkaline phosphatase (CIAP) could be obtained, which is lower than the gold nanoparticle-based colorimetric method.Chapter6will summarize the whole text of this dissertation, assess the work and research results objectively while pointing out the existing deficiencies. Finally we will propose the objectives of ongoing studies and possible researching ideas. |
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