title: 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 IC50values 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.
authors.affiliation: a Department of Biochemistry and Molecular Biology, Faculty of Pharmacy , Helwan University , Cairo , Egypt.
authors.forename: Fathia Zaki
authors.initials: FZ
authors.lastname: El Sharkawi
authors.affiliation: a Department of Biochemistry and Molecular Biology, Faculty of Pharmacy , Helwan University , Cairo , Egypt.
authors.forename: Shaimaa Mohammed
authors.initials: SM
authors.lastname: Ewais
authors.affiliation: b Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.|c Department of Pharmaceutics, Faculty of Pharmacy , Ahram Canadian University , Giza , Egypt.
authors.forename: Rania Hassan
authors.initials: RH
authors.lastname: Fahmy
authors.affiliation: d Department of Biochemistry and Molecular Biology, Faculty of Medicine , Cairo University , Cairo , Egypt.
authors.forename: Laila Ahmed
authors.initials: LA
authors.lastname: Rashed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D053758:Nanoparticles; D051059:PTEN Phosphohydrolase / Q000008:administration & dosage / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D015028:Zein / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D015028:Zein; D051059:PTEN Phosphohydrolase; D020778:Matrix Metalloproteinase 2
keywords: HCC; gene therapy; nanoparticles; PTEN and TRAIL; zein