PTEN and TRAIL genes loaded zein nanoparticles as potential therapy for hepatocellular carcinoma

Abstract

Gene therapy is one of the recent approaches in treatment of hepatocellular carcinoma (HCC). Development of a vector or vehicle that can selectively and efficiently deliver the gene to target cells with minimal toxicity is an urgent demand. In the present study, phosphatase and tensin homolog (PTEN) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) genes were loaded to zein nanoparticles (ZNPs). The formulated PTEN and TRAIL-loaded ZNPs were tested for their in vitro and in vivo potential antitumor efficacy using liver tumor cells (HepG2) and HCC-induced rats as animal model. Also, mRNA expression of p53, VGEF and MMP-2 were carried out as markers of apoptosis, angiogenesis and metastasis in animal liver tissues. The results of the study showed that both PTEN and TRAIL-loaded ZNPs proved anti-proliferative activity against HepG2 cell lines with IC₅₀ values of 0.09, 0.25 µg/ml, respectively. In vivo assay confirmed decrease in mRNA expression of both VEGF and MMP-2 with increased in P53 expression level in liver tissues of the treated animals. Therefore, authors introduced new integration between gene therapy and nanotechnology in the form of PTEN and TRAIL-loaded ZNPs that proved potential to be used in gene therapy for the treatment of HCC.

Keywords:

• HCC; gene therapy; nanoparticles; PTEN and TRAIL; zein

Acknowledgements

Thanks to Dr. Alonzo Ross, University of Massachusetts for providing PTEN-GFP plasmid and Dr. Bingliang Fang, University of Massachusetts for providing pEGFP-TRAIL plasmid.

The authors are indebted to Professor Hany El Shemy Dean of Faculty of Agriculture Cairo University for his excellent support in cytotoxicity assay, and also to colleagues in Department of Microbiology, Faculty of Pharmacy Helwan University for their help in doing bacterial culture.

Disclosure statement

The authors report no conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence, the work in this paper.

The abstract of this paper was presented at the Pharma Middle East 2015 Conference as a power point oral presentation with interim findings.