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Application of Novel ROS sensitive Prodrug on Sunscreen

Liu, Jing
http://orcid.org/0000-0002-8222-1880
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595846650432163

Abstract Details

2020, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
Reactive oxygen species(ROS) are a family of radical and non-radical byproducts of aerobic metabolism. It plays essential roles as secondary signaling molecules in cell proliferation, differentiation, sentence, and apoptosis. Ultraviolet radiation (UVR) overexposure can upregulate ROS in skin cells and results in further damage to deoxyribonucleic acid (DNA), protein, and lipid. As UVR is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and nonmelanoma skin cancer, sunscreen agent was developed to prevent it. The chemoprevention strategy is found and developed since 1976, which is being developed to present. It includes two different types: one is applying the chemical which can absorb or reflect UVR to prevent UVR radiation on the skin surface, the other type affects the metabolism of skin cells to stop the cell damage and malignant initiation. The second category is developing fast in the most recent 20 years to meet the need of human beings. A series of antioxidants and natural products prove to effectively prevent UVR by reducing the ROS level by ROS scavenging or as an inhibitor of the ROS generator. And a ROS-activated prodrug strategy is developed to enhance the selectivity of chemoprevention. The first project was finished by designing a novel ROS-activated moiety attached with apocynin, which is not only an antioxidant but a nicotinamide adenine dinucleotide phosphate oxidase(NOX) inhibitor. Releasing manner about it was studied by high-performance liquid chromatography (HPLC) and mass spectrometry (MS). The skin protection function of it was further proved by gel electrophoresis, dichlorofluorescein diacetate(DCFDA) assay, MTT assay, western blot, and cyclobutane pyrimidine dimers (CPD) quantification. To sum, this prodrug was proved to release the NOX1 inhibitor and protect the DNA from UVR radiation by lowing the ROS level. Considering the drug attached has a controversial mechanism to inhibit ROS generation after releasing it. In the second project, I designed two ROS-activated moieties and attached them with a natural antioxidant and a NOX1 inhibitor. Then releasing manners of each was verified with HPLC and MS. They show the potential to be tested by cells to be further evaluated in the future. In the last project, a new ROS-quantification assay was designed base on the gas chromatography-headspace-mass spectrometry (GCHSMS) system. The probes were designed by attaching a diethylamine to a ROS-active moiety as an analyte. Limit of detection (LOD) and limit of quantification (LOQ) were verified by GCHSMS. Releasing behavior of two different probes were tested by HPLC and GCMS. It proves the potential of them to be further evaluated by cell assay. To sum up, all three projects I worked on the aim to prevent UVR radiation-induced melanoma by lowing ROS. Base on a ROS-active strategy, selectivity, and stability of them are improved. A new quantification assay of ROS is being developed to provide another simple method for further ROS study.
Edward Merino, Ph.D. (Committee Chair)
Ana Luisa Kadekaro, Ph.D. (Committee Member)
David Smithrud, Ph.D. (Committee Member)
Peng Zhang, Ph.D. (Committee Member)
114 p.
Pharmaceuticals
Reactive oxygen species; Ultraviolet radiation; Sunscreen; Cancer; Melanoma; Chemoprevention

Recommended Citations

Citations

  • Liu, J. (2020). Application of Novel ROS sensitive Prodrug on Sunscreen [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595846650432163

    APA Style (7th edition)

  • Liu, Jing. Application of Novel ROS sensitive Prodrug on Sunscreen. 2020. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595846650432163.

    MLA Style (8th edition)

  • Liu, Jing. "Application of Novel ROS sensitive Prodrug on Sunscreen." Doctoral dissertation, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595846650432163

    Chicago Manual of Style (17th edition)

ucin1595846650432163
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This open access ETD is published by University of Cincinnati and OhioLINK.