Effect of tocopherol conjugation on polycation-mediated siRNA delivery to orthotopic pancreatic tumors

Siyuan Tang, Ekta Kapoor, Ling Ding, Ao Yu, Weimin Tang, Yu Hang, Lynette M. Smith, Diptesh Sil, David Oupický

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number213236
JournalBiomaterials Advances
StatePublished - Feb 2023


  • CXCR4 antagonism
  • Intraperitoneal administration
  • Nanoparticles
  • PDAC
  • STAT3
  • siRNA delivery

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Bioengineering


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