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Characterization of aptamer-mediated gene delivery system for liver cancer therapy

Zhongbing Liu1, Xiaoduan Sun1, Shuangli Xiao1,2

  • 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.

Oncotarget
|February 23, 2018
PubMed

Insights

A novel gene therapy system, EpDT3-mediated Ad5-PTEN (EPAP), targets liver cancer cells specifically. This approach enhances antitumor effects while reducing toxicity compared to traditional methods.

Area of Science:

  • Oncology
  • Gene Therapy
  • Biotechnology

Background:

  • Liver cancer presents limited therapeutic options and significant mortality.
  • Recombinant adenovirus expressing the PTEN tumor-suppressor gene (Ad5-PTEN) shows antitumor activity but suffers from nonspecificity and toxicity.
  • Epithelial cell adhesion molecule (EpCAM) is overexpressed in liver cancer, offering a potential therapeutic target.

Purpose of the Study:

  • To develop a targeted gene delivery system, EpDT3-PEG-Ad5-PTEN (EPAP), for liver cancer treatment.
  • To conjugate an EpCAM-targeting RNA aptamer (EpDT3) with Ad5-PTEN using a polyethylene glycol linker.
  • To evaluate the efficacy and specificity of EPAP compared to naked Ad5-PTEN.

Main Methods:

  • Preparation of EPAP via conjugation of EpDT3 with Ad5-PTEN using polyethylene glycol.
  • Confirmation of EPAP preparation using SDS-PAGE, TBE-PAGE electrophoresis, and fluorescence detection.
  • In vitro assessment of EPAP's anti-proliferative and anti-migratory effects on HepG2 cells.
  • In vivo evaluation of EPAP's selective targeting of EpCAM-positive HepG2 cells.

Main Results:

  • Successful synthesis and confirmation of the EPAP gene delivery system.
  • EPAP demonstrated significant anti-proliferative and anti-migratory activities against HepG2 liver cancer cells.
  • EPAP exhibited selective and precise targeting of EpCAM-positive HepG2 cells in vivo.

Conclusions:

  • EPAP represents a promising targeted gene therapy strategy for liver cancer.
  • The EpDT3-mediated delivery system overcomes limitations of naked Ad5-PTEN, enhancing antitumor efficacy.
  • EPAP warrants further investigation as a novel therapeutic agent for malignant liver cancer.
Keywords:
PTENadenovirusaptamer EpDT3cell migrationliver cancer

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