Date of Award
12-17-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biology
First Advisor
Nawab Ali
Abstract
Pancreatic cancer remains one of the most lethal malignancies, with a five-year survival rate below 5%. While rapamycin (Rap) has demonstrated therapeutic potential, its clinical utility is hampered by systemic toxicity. To address this limitation, this study developed a targeted nanocarrier system using gold nanospheres (AuNPs) functionalized with the Epidermal Growth Factor Receptor (EGFR) peptide GE11 for the specific delivery of Rap to pancreatic cancer cells. It is to note that pancreatic cancer overexpresses EGFR. The AuNP–GE11–Rap conjugates were successfully synthesized and characterized using physico-chemical techniques, which confirmed peptide conjugation and drug loading. In vitro studies using PANC-1 cells demonstrated that the GE11 ligand facilitated efficient cellular internalization via EGF- receptor-mediated endocytosis, leading to lysosomal localization and high intracellular Rap accumulation. The targeted conjugate exhibited significantly enhanced anticancer efficacy compared to controls. Treatment with AuNP–GE11–Rap inhibited cell proliferation and induced apoptosis, as evidenced by caspase activation, mitochondrial membrane potential dysfunction, and elevated reactive oxygen species. Furthermore, global proteomic profiling by LC–MS/MS analysis revealed that the conjugate induced broad modulation of critical signaling pathways, including suppression of oncogenic PI3K/Akt/mTOR and STAT3 signaling, and upregulation of tumor-suppressor pathways such as p53. Proteins linked to metastasis and angiogenesis were also downregulated. In conclusion, this research establishes that the EGFR-targeted AuNP platform not only serves as an efficient Rap carrier but also actively perturbs cellular homeostasis to enhance pancreatic cancer cell killing. The multi-faceted mechanism of action, coupled with the potential for reduced systemic toxicity, underscores the high therapeutic promise of this nanocarrier approach for pancreatic cancer.
Recommended Citation
Oluremi, Adeolu, "Targeting Pancreatic Cancer with Rapamycin-Loaded Gold Nanoparticles Conjugated to EGF Peptide: Studies on Cytotoxicity and Uptake Mechanisms Aided by Proteomic Analysis" (2025). Theses and Dissertations. 1309.
https://research.ualr.edu/etd/1309
