Files
Abstract
Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The main goal of this project is to develop a target-specific stimuli-responsive MSN based drug delivery system for the simultaneous delivery of cisplatin and gemcitabine. Both drugs were chemically attached to the MSNs via stimuli-responsive linkers that respond to the high reducing environment and low pH characteristic of cancer cells. The MSN materials fabricated in this work were successfully synthesized and characterized with a wide variety of spectroscopic and microscopic techniques. The loading of cisplatin and gemcitabine and their release profile under high reducing conditions were determined using atomic absorption (AA) and UV-vis spectroscopy, respectively. In vitro toxicity studies were performed on human cervical cancer (HeLa) cells in the presence of different ratios of cisplatin/gemcitabine drugs to determine the best ratio to kill HeLa cells. Based on this data, MSN materials carrying individual drugs and the corresponding combinatorial nanoparticles were fabricated and their in vitro cytotoxicity evaluated in HeLa and pancreatic cancer cells (AsPC1 and BxPC-3). The next step in this project was to further modify with folic acid to enhance its targeting ability toward cancer cells overexpressing folate receptors.