Carbon-Based Nanomaterials and their Medical Applications
Samuel, Errol Loïc Graeme
Tour, James M.
Doctor of Philosophy
The Tour lab has previously demonstrated that antibody-targeted drug-loaded carbon nanoparticles, called PEGylated hydrophilic carbon clusters (PEG-HCCs), can be utilized for cancer-specific drug delivery both in vitro and in vivo. In this work, we append a range of receptor-binding peptides to PEG-HCCs, and show that these peptidyl-PEG-HCCs have enhanced utility in killing a number of different cancers in vitro and in vivo. Moreover, we can potentiate cancer-specific toxicity by using peptide-targeted PEG-HCCs to deliver xenobiotic drug pump inhibitors to cancer cells simultaneously with chemotherapy. With the plethora of drug delivery vehicles currently under study, we have diverted our attention to capitalizing on the intrinsic properties of our PEG-HCCs; most notably, their antioxidant activity. PEG-HCCs show high capacity to annihilate reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, show no reactivity toward nitric oxide, and can be functionalized with targeting moieties without loss of activity. PEG-HCCs therefore offer an exciting new area of study for treatment of numerous ROS-induced human pathologies. Furthermore, a new class of carbon particles developed in the Tour lab, graphene quantum dots derived from coal, possess the same properties and are even more promising, given their inexpensive starting material and simple preparation. In many neurodegenerative diseases, inflammation is associated with an increase in ROS. We have found that PEG-HCCs are immunomodulatory, reducing inflammation by suppression of the effector memory T cell response. Further, PEG-HCCs can be modified in order to visualize them both in vitro and in vivo using magnetic resonance imaging (MRI). Our data, along with previous work, demonstrates potential T cell tracking utility of our nanoparticles and their ability to modulate inflammation. Finally, a different nanostructured material, graphene nanoscaffolds prepared form graphene oxide, was explored as a bioscaffold for neuronal regeneration after spinal cord injury (SCI). The graphene nanoscaffolds adhered well to the spinal cord tissue and there was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Thus, it may provide a scaffold for the ingrowth of regenerating axons after SCI.