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 Gd3+-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.