Carbon Nanomaterials and Their Derivatives for Traumatic Brain Injury and Other Biomedical Applications
Tour, James M
Doctor of Philosophy
Carbon nanomaterials possess unique chemical and functional properties allowing for their applications across a variety of fields including medicine, energy, materials, mechanics and more. Herein, the synthesis of poly(ethylene glycol) hydrophilic carbon clusters (PEG-HCCs) and poly(ethylene glycol) graphene quantum dots (PEG-GQDs), as well as their biomedical applications as antioxidants is described. Although use of antioxidants has been aimed at reducing the presence of reactive oxygen and nitrogen species (ROS and RNS), success in clinical trials has been disappointing. Traumatic brain injury (TBI) is a leading cause of death and disability in the United States, especially when complicated by secondary trauma, such as hemorrhagic hypotension. Oxidative stress is a prominent feature of TBI that can result in loss of cerebral blood flow (CBF) to the brain causing an increased susceptibility to hypotension and intracranial hypertension. The development of PEG-HCCs through the oxidation of single-walled carbon nanotubes (SWCNTs) has shown its capability to quench SO and HO•. PEG-HCCs are soluble, non-toxic potent antioxidants that are stable in biological media. They can be administered through IV and have been tested in a rat model of TBI. Additionally, the application of PEG-HCCs in a mouse Alzheimer’s disease model was also explored. PEG-HCCs have demonstrated the ability to restore CBF to the brain after injury when administered through IV. Additionally, intranasal administration of PEG-HCCs has been shown to reduce amyloid precursor protein (APP) in the brain. PEG-GQDs, similar to PEG-HCCs, was developed as a derivative and cost-effective antioxidant carbon nanomaterial for the treatment of TBI. Using coal as a starting material (bituminous and anthracite) GQDs were characterized and modified with poly(ethylene glycol). Their intrinsic and chemical properties were evaluated also showing the ability to quench superoxide (SO) and hydroxyl radical (HO•). PEG-GQDs were tested in a rat model of TBI and demonstrated the ability to restore CBF to the brain after injury. PEG-GQDs are water-soluble, non-toxic antioxidants that can be administered intravenously. Overall, PEG-HCCs and PEG-GQDs were studied in vitro and in vivo animal models with novel results that bear further investigation. The need for the development of robust therapy to address oxidative stress is necessary to effectively treat and eliminate damage that otherwise results in devastating outcomes for patients on personal, social and societal levels.
Traumatic Brain Injury; Carbon Nanomaterials; Antioxidants; Oxidative Stress