Fullerene and Boron Nitride Nanomaterials for Biomedical Applications
Wilson, Lon J
Doctor of Philosophy
This thesis presents an evaluation of the potential of two new nanoparticles as biomedical agents, as well as an acid digestion method for exceptionally stable metal-doped nanoparticles, such as for the burgeoning field of boron nitride nanomaterials. With the birth of nanotechnology, researchers have explored functionalizing nanoparticles for various medical applications and have shown these nanoparticles to have many attractive properties. The present work strives to further understand the structure-function relationships for such biomedical nanomaterials. This thesis examines two very different nanomaterials – C60 fullerenes and boron nitride nanotubes (BNNTs) – and aims to answer key questions related to their biological potential. In the first part of the thesis, a biocompatible C60 fullerene was functionalized to be radiolabeled in order to examine its biodistribution in vivo using copper-64 positron emission tomography (PET). These studies showed that the resultant fullerene material was cleared rapidly and almost exclusively by the kidneys within three hours. This finding is in stark contrast to many other biocompatible fullerene materials in the literature with completely different biodistribution profiles and extremely long clearance times (> 100 hours). These data clearly demonstrate that fullerene-based drug delivery agents must be approached rationally to design materials that have predictable and favorable biodistribution and pharmacokinetic profiles. In the second part of the thesis, BNNTs were loaded with gadolinium chelates rendering the modified BNNT material a magnetic resonance imaging (MRI) contrast agent. However, the high stability of BNNTs prohibited accurate quantification of the metal content using inductively-coupled plasma (ICP) techniques because of incomplete digestion and subsequent release of Gd3+ ions for quantification. Various acid digestion methods were explored and optimized to achieve complete digestion of the BNNT material only in the case of concentrated boiling perchloric acid at 203 C. The gadolinium chelate loading capacity of the BNNT material was optimized and its MRI activity determined and studied. With the development of the perchloric acid preparation method, researchers now have a proven tool to quantify metal content of any new metal-doped BNNT material. This robust and time-dependent oxidation method also offers the potential of providing new BNNT materials with beneficial defect sites for further functionalization.