Type
Text
Type
Dissertation
Advisor
Brouzes, Eric | Sitharaman, Balaji | Chan, Mei Lin | Truman, Jean-Philip.
Date
2016-12-01
Keywords
Cancer, Ceramide, Drug Delivery, Graphene, Nanoparticle, Sphingolipid | Biomedical engineering
Department
Department of Biomedical Engineering
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76975
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
In recent years there has been a growing appreciation for the active functions certain lipids have in cellular metabolism. These "bioactive lipids" have been found to be an important part of many cell signaling processes. In particular, the bioactive sphingolipid ceramide has emerged as an important player in cancer biology. Dysregulation of ceramide metabolism has been shown to impart resistance to drug and radiation treatment in certain types of cancer, with low levels of specific ceramide species conferring resistance to apoptosis. It has also been shown that restoring levels of these ceramides in cancer cells through exogenous delivery also restores sensitivity to radiation and drug treatment. As such, the exogenous delivery of ceramide to represents an untapped therapeutic target for the treatment of resistant cancers. However, as a lipid, ceramide is extremely hydrophobic and has virtually no solubility in aqueous solution; it requires a delivery system for successful entry into cells. Current methods of ceramide delivery have serious drawbacks, and as a result, there is currently no clinically approved method for the therapeutic delivery of ceramide. In this work, we present the use of oxidized graphene nanoribbons (O-GNRs) derived from multi-walled carbon nanotubes as a delivery system for ceramide. We developed a novel method for the noncovalent reversible loading of ceramide onto O-GNRs. Using this method, we were able to load significant amounts of both short chain and long chain ceramides onto O-GNRs. We found that the short-chain C6 ceramide was able to directly induce high levels of apoptosis in cancer cells when loaded onto O-GNRs. We also found that long chain C16 and C24 ceramides were able to modulate the resistance of cancer cells to drug and radiation treatment when loaded onto O-GNRs. However, we found that O-GNRs have significant biological effects that interfere with the effects of ceramide on drug and radiation treatment, suggesting a critical need to optimize the properties of these nanoparticles for use with ceramide. Despite these limitations, these results represent a promising first step on the path to therapeutic delivery of ceramide. | 191 pages
Recommended Citation
Suhrland, Cassandra, "Oxidized Graphene Nanoparticles as a Delivery System for the Bioactive Sphingolipid Ceramide" (2016). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2841.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2841