Shape dependent iron oxide nanoparticles for simultaneous imaging and therapy
The primary focus of this dissertation is to explore the use of shape dependent iron oxide nanoparticles as magnetic resonance imaging contrast agents. In addition to biocompatibility, nanoparticles provide a foundation for implementing imaging guided drug delivery systems. We begin with the synthesis of iron oxide nanoparticles of varying sizes and shapes. Specifically, large (>4 nm) spherical particles, ultrasmall (<4 nm) nanoparticles, and ultrathin (2x20 nm) nanowires were synthesized by thermal decomposition of an iron oleate precursor. To render the nanoparticles biologically compatible, a phase transfer step was necessary to transfer nanoparticles from organic solvents aqueous phase. Insufficient or incomplete ligand exchange of the ultrasmall nanoparticles could result in aggregation and a loss of the paramagnetic properties. Here we were able to successfully coat the nanoparticles with several biologically compatible ligands while maintaining the paramagnetic properties for T1 MRI contrast agents. Furthermore, we explored the cellular uptake behaviors of the subnanometer ultrasmall nanoparticles and ultrathin nanowires. The nanoparticles were functionalized with tannic acid and incubated with HepG2 cells. The shape dependent cellular uptake was quantified, and the ultrasmall nanoparticles exhibited a much higher cellular uptake than the ultrathin nanowires. The high cellular uptake of the ultrasmall nanoparticles may be ideal for stem cell labelling, however the low blood circulation time (<15 min) limited their use, in vivo. In order to increase the circulation time, the size must be increased without altering the magnetic properties of the nanoparticles. Therefore, the ultrasmall nanoparticles were trapped in a bovine serum albumin matrix using protein desolvation. Using the protein matrix, nanoparticles were clustered together, free from aggregation, in a water rich environment allowing for the clusters to maintain the positive, T1 contrast. Encapsulation of the nanoparticles in proteins increased the in vivo blood circulation time from 15 min to over 2 hours. Finally, we demonstrated that both small molecule and protein drugs may be loaded into the clusters. The drug loading and release was studied using fluorescent dyes as a model. The drugs could be released through two mechanisms, enzymatic degradation, or physically released using ultrasound. These studies open up the possibility to both deliver drugs to targeted locations, as well as monitor the distribution, localization, and release of the drugs, noninvasively, in vivo, using MRI.