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Radioprotectant Ceria Nanoparticles Drug Delivery System to Reduce Reactive Oxygen Species Levels and Mitigate Spaceflight Osteopenia

In the extreme environment of space, radiation induced health issues is a major concern. The ability to induce higher levels of free radicals and reactive oxidative species (ROS) are factors to be addressed. Ceria nanoparticles (CNPs) can provide a means to scavenge ROS through regenerative redox coupling that occurs on the surface and acts as a radioprotectant. Additionally, the defect levels in CNP can be categorized by the Ce3+/Ce4+ ratio with a high ratio indicating superoxide scavenging, a radical species with high oxidative potential. However, engineering a specialized Ce3+ NP often requires a harsh reducing agent. We hypothesized a wet-chemical synthesis utilizing both reducing and non-reducing sugars to engineer stable CNPs with high Ce3+ state. This sustainable process uses simple sugars to ensure high biocompatibility while maintaining the specific vacancy density found in Ce3+ dominant CNP. X-Ray photoelectron spectroscopy (XPS) show that the reducing sugars allows for nearly 70/30 Ce3+/Ce4+ ratio compared to non-reducing sugars. This high Ce3+/Ce4+ ratio of CNPs can be useful in scavenging ROS in space radiation applications. In addition, typical drug molecules utilize biopolymers which can increase ROS under the ionizing radiation environments found in space. To improve the drug viability, we hypothesized CNPs conjugated to drugs as a viable solution. Current results indicate high Ce3+ structural confirmation of ceria nanoparticles using a wet-chemical synthesis. The synthesized nanoparticles were then conjugated with risedronate, a third-generation bisphosphonate. Microwave radiation studies indicated that CNP was able to be used as a radioprotectant as it prevented changes in drug chemistry as detected by UV/Vis spectra after exposure to microwave radiation. Finally, in vitro human mesenchymal stem cell results from alkaline phosphatase (ALP) and Alizarin red S (ARS) assays, suggest potential for the conjugates to differentiate cells. The mechanism for radioprotective ability can be attributed to the high Ce3+ state.

Identiferoai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2506
Date01 January 2023
CreatorsBabu, Balaashwin
PublisherSTARS
Source SetsUniversity of Central Florida
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceElectronic Theses and Dissertations, 2020-

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