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

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 th...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials advances 2023-02, Vol.145, p.213236-213236, Article 213236
Main Authors: Tang, Siyuan, Kapoor, Ekta, Ding, Ling, Yu, Ao, Tang, Weimin, Hang, Yu, Smith, Lynette M, Sil, Diptesh, Oupický, David
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Pancreatic Ductal - drug therapy
Carcinoma, Pancreatic Ductal - genetics
Humans
Mice
Pancreatic Neoplasms
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
RNA, Small Interfering - genetics
Tissue Distribution
Tocopherols - pharmacology
Tocopherols - therapeutic use
Tumor Microenvironment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2772-9508
2772-9516
2772-9508
DOI:10.1016/j.bioadv.2022.213236