Carbon nanomaterials and their small molecule analogues for biomedical applications
Nilewski, Lizanne G.
Tour, James M
Doctor of Philosophy
Carbon nanomaterials possess unique structural features that give them interesting properties and reactivity for applications in medicine, electronics, materials, catalysis, and more. Herein, the synthesis of PEG-HCCs, PEG-GQDs, and small molecule analogues of these functionalized carbon nanomaterials, as well as their biomedical applications as drug delivery vehicles and antioxidants, are described. PEGylated hydrophilic carbon clusters (PEG-HCCs) are non-toxic water-soluble carbon nanomaterials synthesized by the oxidation of single walled carbon nanotubes (SWCNTs). It is shown that PEG-HCCs can be non-covalently loaded with drugs and covalently modified with various targeting peptides to deliver drugs selectively to glioblastoma cells in vitro and tumors in vivo. It was also found that sensitive imaging of tumors over normal tissue could be achieved by loading the peptide-targeted PEG-HCCs with fluorescent dyes instead of drugs. PEG-HCCs are also powerful antioxidants that are capable of quenching superoxide and hydroxyl radicals. The application of PEG-HCCs as immunomodulators for the treatment of multiple sclerosis (MS) and other T cell-mediated autoimmune disorders like rheumatoid arthritis, was explored. PEG-HCCs were observed to selectively target T cells over other immune cells, and were found to modulate T cell activity by inhibiting proliferation, and they significantly reduced the severity of symptoms in a rat model of MS. In addition to PEG-HCCs, another class of antioxidant carbon nanomaterials, coal-derived graphene quantum dots (GODs) and PEG-GQDs, was developed. These highly oxidized redox active materials were characterized and tested with respect to superoxide and hydroxyl radical activity. PEG-GQDs were also studied in a rat model of traumatic brain injury. It was found that GQDs and PEG-GQDs possess similar characteristics, reactivity, and antioxidant abilities to the HCCs both in cell-free systems and in vivo. Furthermore, perylene diimides (PDIs) and naphthalene diimides (NDIs) were synthesized to mimic the structure and antioxidant activity of the HCCs and GQDs. The PDIs in particular were found to mimic both HCCs and the enzyme SOD by catalyzing the dismutation of superoxide into O2 and H2O2. PDIs were studied with respect to their antioxidant properties, and modified PDIs were also synthesized to modulate their redox properties. Finally, PDIs were studied as antioxidants in in vitro T cell experiments, where it was found they have similar behavior to the PEG-HCCs as potential immunomodulators. Lastly, another class of biologically active targeted molecules was studied for the treatment of cancer. Light-activated nanomachines based on the previous work of the Tour lab were selectively targeted to cancer cells using short peptides, similar to the targeting of PEG-HCCs to tumors. These peptide-targeted nanomachines were shown to associate with their intended target cancer cells over control cells, and once bound to the membranes of target cells, the nanomachines were activated using UV light. This induced MHz rotation of the “motor” moiety and mechanically disrupted the cell membrane leading to cell death. Overall, the PEG-HCCs, PEG-GQDs, PDI/NDI small molecules, and nanomachines were studied in cell-free systems, in vitro, and in vivo with promising results that warrant continued investigation of their mechanism and applications.