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Updated: Aug 17, 2025
Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
Effect of tocopherol conjugation on polycation-mediated siRNA delivery to orthotopic pancreatic tumors
Siyuan Tang1, Ekta Kapoor1, Ling Ding1
1Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a five-year survival rate of around 10 %. CXCR4 and STAT3 display crucial effects on proliferation, metastasis, angiogenesis, and formation of immunosuppressive microenvironment in pancreatic tumors. Here, we have tested the hypothesis that conjugation of α-tocopherol (TOC) to a polycation (PAMD), synthesized from CXCR4-antagonist AMD3100, will improve delivery of therapeutic siRNA to silence STAT3 in PDAC tumors. PAMD-TOC/siSTAT3 nanoparticles showed superior anti-cancer and anti-migration performance compared to the parent PAMD/siSTAT3 nanoparticles in both murine and human PDAC cell lines. The biodistribution of the nanoparticles in orthotropic mouse KPC8060 and human PANC-1 models, indicated that tumor accumulation of PAMD-TOC/siRNA nanoparticles was improved greatly as compared to PAMD/siRNA nanoparticles. This improved cellular uptake, penetration, and tumor accumulation of PAMD-TOC/siSTAT3 nanoparticles, also contributed to the suppression of tumor growth, metastasis and improved survival. Overall, this study presents a prospective treatment strategy for PDAC.
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