Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo

Journal of Controlled Release : Official Journal of the Controlled Release Society
Shuangli XiaoZhirong Zhong

Abstract

A recombinant adenovirus carrying the tumor suppressor gene PTEN (Ad5-PTEN) is an effective antitumor agent against liver cancer. But the application of Ad5-PTEN has been greatly hindered by its auto-immunogenicity, non-specific toxicity to normal tissues, as well as poor stability in blood stream because of neutralizing antibody. Epithelial cell adhesion molecule (EpCAM) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in liver cancer. An RNA aptamer EpDT3 could specially bind with EpCAM and target EpCAM-positive cells. Therefore, we hypothesized that developing a novel gene delivery system of EpDT3-modified Ad5-PTEN could overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on hepatocellular carcinoma. We took polyethylene glycol (PEG) as a linker to conjugate EpDT3 with Ad5-PTEN to prepare EpDT3-PEG-Ad5-PTEN (EPAP) by simple chemical synthesis method. We found that the stability of this novel gene delivery system in human blood serum increased about 16-fold compared to the naked adenovirus. Meanwhile, EPAP enhanced gene expression and cellular uptake in HepG2 cells, and showed significant inhibition in cell proliferation and cell migration agai...Continue Reading

Citations

Dec 17, 2019·Therapeutic Delivery·Katherine E Redd BowmanCarol S Lim
Oct 20, 2018·International Journal of Molecular Sciences·Jing LiQi Sun
Jul 26, 2019·World Journal of Gastroenterology : WJG·Guo-Qing ZhangYong-Xiang Zhao
Dec 18, 2019·International Journal of Pharmaceutics·Muhammad Yasir AliUdo Bakowsky
Jan 1, 2021·ACS Applied Materials & Interfaces·Jiayao LyuZhirong Zhong

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