Date of Award
Spring 5-12-2017
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Dr. Santimukul Santra
Second Advisor
Dr. Khamis Siam
Third Advisor
Dr. Irene Zegar
Fourth Advisor
Dr. Jian Hong
Keywords
Lactonic Sophorolipid, Ganetespib, HDAC Inhibition, Antioxidant Nanoceria, NSCLC Therapy, Combination Therapy
Abstract
Lactonic sophorolipids (LSL) are a class of enzymatically modified glycolipids known to have HDAC inhibition activity and anticancer properties. Ganetespib (GT), an Hsp90 inhibitor, is known for its superior antitumor activity in several K-RAS mutant Non-Small-Cell Lung Cancer (NSCLC) cells. In this study, a new anti-oxidant nanoplatform is formulated using the combination of these two drugs, LSL and GT, in order to target both HDAC inhibition and Hsp90 signaling pathways in NSCLC. Nanoceria (NC) is an excellent redox platform will be specifically used to supplement the therapeutic potency of these drugs in the effective treatment of NSCLC. We hypothesized that the therapeutic efficacy of GT will be synergistically accelerated by the HDAC inhibition and redox activity of LSL and NC, respectively. For this, polyacrylic acid-coated nanoceria (NC-COOH) is synthesized using solvent precipitation method and folic acid is conjugated using ‘click’ chemistry in order to target NSCLC and to minimize adverse side effects. As a result of combination therapy, enhanced ROS production is detected and more than 80% reduction in the cell viability is recorded within 24 h of incubation. Migration assays indicated that the highly metastatic nature of NSCLC is successfully restricted upon treatment of these drugs-loaded functional nanoceria. In addition, various cell-based assays including detection of apoptosis and necrosis, HDAC inhibition, MTT and fluorescence microscopy are performed to validate the highly effective combination therapy of NSCLC. Together, our results represent for a unique combination of drugs and personalized delivery system for the effective treatment of K-RAS driven undruggable NSCLC.
Recommended Citation
Naz, Shuguftha Ms, "MOLECULARLY TARGETED NANOMEDICINE: ROLE OF HSP90 INHIBITOR AND SOPHOROLIPIDS IN THE TREATMENT OF LUNG CANCER" (2017). Electronic Theses & Dissertations. 376.
https://digitalcommons.pittstate.edu/etd/376
