Author ORCID Identifier
Document Type
Dissertation
Date of Award
2023
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Grigoriy Sereda
Abstract
This dissertation delves into the innovative application of mesoporous silica nanoparticles (MSNs) for targeted drug delivery in colorectal cancer (CRC), one of the most prevalent and deadly forms of cancer worldwide. The initial focus of the research is on developing enzyme-responsive MSNs loaded with veratridine (VTD), an alkaloid derived from natural sources that demonstrates potent anticancer activity. The nanoparticles have been engineered to deliver VTD selectively to CRC cells, releasing the payload upon being exposed to specific enzymes primarily secreted by these cells. This strategy has dual advantages of amplifying the anticancer effects while minimizing potential side effects on healthy cells, maximizing the overall therapeutic efficacy. Building on this groundbreaking work, the research extends to another plant-based compound, eugenol (EUG), encapsulated within enzyme-responsive nanoparticles. EUG is renowned for its anti-growth and apoptotic properties against various malignant tumors. The newly developed nanoparticles are shown to significantly decrease metastasis potential and resistance in CRC cells. Simultaneously, they reduce the adverse side effects commonly seen in normal cells, thus adding another promising tool to our anticancer arsenal. The research further broadens the scope by exploring a dual enzyme and pH-responsive MSNs/hydroxyapatite hybrid nanostructure. This smart system responds not only to CRC-specific enzymes but also to the acidic microenvironment typically found in tumors. Consequently, it enhances localized drug concentration and augments drug delivery efficiency. The final part of the dissertation investigates the impact of PEGylation on the colloidal stability and drug-loading capacity of MSNs. While PEGylation improves the stability of MSNs, more investigation is required to fully understand its implications on drug loading and controlled release. In conclusion, this work contributes significant insights and offers promising prospects for improving therapeutic strategies and patient outcomes in CRC through advanced nanoparticle delivery systems.
Subject Categories
Chemistry | Materials Science and Engineering | Nanoscience and Nanotechnology
Keywords
Anti-cancer drug molecules, Colorectal cancer, Drug delivery, Mesoporous silica nanoparticles, Metastasis, Nano drug carriers
Number of Pages
157
Publisher
University of South Dakota
Recommended Citation
Wijewantha, Nisitha Lakmal Wellala, "DEVELOPING MESOPOROUS SILICA NANOPARTICLE-BASED STIMULI-RESPONSIVE NANOCARRIERS FOR DELIVERY OF SMALL MOLECULE THERAPEUTICS AGAINST COLON CANCER CELLS" (2023). Dissertations and Theses. 172.
https://red.library.usd.edu/diss-thesis/172
Included in
Chemistry Commons, Materials Science and Engineering Commons, Nanoscience and Nanotechnology Commons