Presentation: 2024 ND EPSCoR Annual conference
November 21, 2024, Alerus Center, Grand Forks, North Dakota
Development of hypoxia-responsive polymersomes for drug delivery to pancreatic ductal adenocarcinoma (PDAC) cells
Chukwuebuka
Ozoude
Doctoral Student
North Dakota State University
Co-authors: Chukwuebuka Ozoude, Department of Pharmaceutical Sciences, NDSU; Connor Edvall, Department of Pharmaceutical Sciences, NDSU; Shubhashri Ambhore, Department of Pharmaceutical Sciences, NDSU; Rayat Hossain, Department of Pharmaceutical Sciences, NDSU; Sanku Mallik, PhD, Department of Pharmaceutical Sciences, NDSU
Session
Poster Session A
Poster #68
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hypoxia is a significant characteristic of solid tumors. Hypoxic conditions generated by the growth of these tumors enable the cancer cells to proliferate, metastasize, and evade chemotherapy. We propose that either a CXCR4 inhibitor (AMD3100) or a STAT3 inhibitor (narciclasine) could decrease cancer stemness and increase the effectiveness of the anticancer drug gemcitabine (GEM) in killing the hypoxic PDAC cells. Hypoxia-responsive polymersomes (HRPs) encapsulating these inhibitors deliver synergistic combinations in PDAC tumors. Synergy studies were conducted to determine the concentrations of the drugs that would be most effective on the PDAC cell lines. A hypoxia-responsive polymer containing polyethylene glycol-diazobenzene-polylactide was synthesized and characterized. Subsequently, drug-encapsulated, hypoxia-responsive polymersomes were formulated. The in vitro studies showed that the synergistic drug combinations improved anticancer activity in 2D assay and 3D cultures of PDAC cells. HRPs containing encapsulated drugs have the potential to penetrate pancreatic tumors to deliver their cargo for synergistic anticancer activity.