Nanomaterials for X-ray imaging and image-guided therapy applications
Hernandez Rivera, Mayra
Wilson, Lon J.
Doctor of Philosophy
In recent years, nanomaterials have been explored for a wide range of different applications. Their tunable size and composition allow them to cross cellular membranes, and therefore, various nanomaterials have been used for a diversity of medical applications such as drug, gene and protein delivery, as well as for diagnostic tools in the form of imaging agents. This work presents the study of two new carbon nanotube (CNT)-based materials as radiocontrast agents for stem cell labeling and imaging. X-ray-based imaging modalities are the most used and readily available diagnostic imaging tools in the clinic today; however, this technology is not the conventional method for imaging and tracking of stem cells. Hence, this work introduces the use of CNT materials as contrast agents (CAs) for X-ray computed tomography (CT) imaging, as an alternative to magnetic resonance imaging (MRI), which is currently the technology of choice for this purpose. The first material described in this thesis, termed Bi@US-tubes, consists of ultra-short CNTs (US-tubes, 20-80 nm), loaded with bismuth ions. Bi@US-tubes contain 2-3% bismuth by weight and its use as an intracellular CA for mesenchymal stem cells (MSCs) has been studied. As a second generation material, Bi4C@US-tubes has also been prepared, characterized, and used to intracellularly label MSCs. Bi4C@US-tubes are derived from US-tubes and Bi(III)-oxo salicylate clusters which localize at defect sites and along the sidewalls of the US-tubes. Bi4C@US-tubes contain 20% bismuth by weight, and therefore, this new material exhibits higher X-ray attenuation than Bi@US-tubes. The labeled MSCs showed high viability regardless of whether Bi@-US-tubes or Bi4C@US-tubes were used as the intracellular CA. The proliferation, differentiation, and other properties of the labeled MSCs were also studied, which showed no major differences when compared to control cells. The final part of this thesis describes the preparation and characterization of a new formulation containing an anticancer drug, heparin, and an iron oxide nanoparticle, all of which are FDA-approved compounds. The three components interact to one another by electrostatic interactions to form a nanocarrier that can be manipulated and targeted by strong external magnetic fields. The release of the drug, doxorubicin, from the nanocarrier was found to be pH-dependent, with faster release occurring under acidic conditions. This new formulation has the potential to be used in the clinic as an image-guided therapy when using magnetic targeting in conjunction with MRI tracking.
carbon nanotubes; X-ray imaging; mesenchymal stem cell; bismuth; iron oxide