There are insufficient achievements in the field of cancer diagnosis and treatment for new dual agents, which would provide health care specialists the ability to simultaneously image patients’ cancerous tissues as well as treat the diseases. Prussian blue (ferric hexacyanoferrate) is a nontoxic FDA approved compound used clinically as an antidote for thallium and radioactive cesium poisoning. In this thesis development of simple methods for the synthesis of biocompatible Prussian blue nanoparticles (PBNPs) and its analogues as well as their applications for magnetic resonance imaging (MRI) contrast agents and drug delivery have been studied. The extensive magnetic properties investigations show that Prussian blue nanoparticles and gadolinium doped analogue nanoparticles significantly shorten the T1 relaxation time in aqueous solution and in HeLa cells treated with PBNPs, demonstrating their potential use as MRI contrast agents. Although the relaxivity values of Prussian blue nanoparticles are approximately an order of magnitude lower than the typical commercial Gd 3+-based T1 contrast agents but it is found to be comparable to the values obtained for the MnO nanoparticles-based T1 agents. In order to provide high contrast, gadolinium doped Prussian blue nanoparticles (Gd-PBNPs) were prepared. It was also found that the Gd-PBNPs can shorten the T1 relaxation time significantly and provide potential use for clinical applications. In order for Prussian blue and its analogues nanoparticles to be concurrently utilized as drug delivery agents they must be biocompatible and capable of crossing the plasma membrane. Therefore, Prussian blue nanoparticles and related analogues were synthesized and functionalized by carboxylic acids such as citric acid as capping agents to control size distribution.
To study the intracellular uptake of Prussian blue and analogue nanoparticles, their surfaces were functionalized separately with the small molecule dyes such as 5-carboxyfluorescein and Alexa Fluor® 350 cadaverine, as well as the anticancer agent. Confocal fluorescence imaging of HeLa cells treated with the functionalized nanoparticles shows fluorescent signals in the cells suggesting intracellular uptake of the Prussian blue and Gd-PB nanoparticles. The HeLa cells internalized Prussian blue nanoparticles and gadolinium-containing Prussian blue nanoparticles could also enhance the T1 MRI contrast. The results clearly show that these nanoparticles can be used as an effective T1 contrast agent for cellular imaging. Functionalized Prussian blue nanoparticles and related analogues with both MRI contrast and drug delivery capabilities may become powerful dual agents for simultaneous cancer treatment and assessment of treatment effectiveness.
Keywords: Prussian blue, coordination polymers, gadolinium, nanoparticles, imaging agents, contrast agents, magnetic resonance imaging, molecular imaging, relaxivity, drug delivery, magnetic properties.
|Advisor:||Huang, Songping D.|
|Commitee:||Huang, Songping D.|
|School:||Kent State University|
|Department:||College of Arts and Sciences|
|School Location:||United States -- Ohio|
|Source:||MAI 49/01M, Masters Abstracts International|
|Subjects:||Analytical chemistry, Inorganic chemistry|
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