Diabetes patients are increasingly suffering from wound-healing impairments coupled with other severe medical conditions. High levels of oxidative stress and proinflammatory cytokines are predominant pathologic characteristics of diabetic wounds. Applying microRNA (miRNA) in gene therapy often successfully treats various disorders by generating highly specific bio-responses. Studies revealed that microRNA146a (miR146a), a regulator of inflammation, is downregulated in diabetic wounds. However, miR203 is found to be highly-expressed in diabetic foot ulcers in positive correlation with disease severity. We have synthesized Cerium oxide nanoparticles (CNPs) since they are used in various biomedical applications due to their high enzyme-mimetic activities and reactive oxygen species (ROS) scavenging abilities. In the present work, two studies are presented. The first study examines whether CNPs can stabilize and protect surface-bound miR146a from oxidative damage under excess ROS exposure. We assessed the relative performance of a miR146a-conjugated CNP formulation (CNP-miR146a) by comparing against two other nanoparticle compositions widely used in nanomedicine: gold and silica. Results from material characterizations and electroanalytical studies demonstrated stable catalytic responses of CNP-miR146a toward ROS and CNPs' ability to protect miR146a from oxidative damage, while the other formulations were relatively ineffective. In the second study, different copper concentrations were incorporated into the nanocrystalline CNP lattice. The defects created in CNPs and the differences between produced formulations were evaluated through XPS, TEM, and XRD. An electrochemical biosensor was developed using the electrochemical charge transfer properties of copper-modified CNP formulation to determine miR203 concentration. Biosensor function was assessed by electroanalytical studies: showing a detection range from 10 μM down to the detection limit 1.73 fM. The present studies demonstrated that the surface catalytic activities of CNP formulations can mediate preservation of miRNA functional integrity and allow quantitative detection of miRNA in an electrochemical biosensor platform. Together, these studies suggest unique value for CNPs in miRNA-based biotechnologies.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2552 |
| Date | 01 January 2023 |
| Creators | El Ghzaoui, Chaimae |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
Page generated in 0.0022 seconds