Antitumor effect of human TRAIL on adenoid cystic carcinoma using magnetic nanoparticle–mediated gene expression

To overcome treatment limitations of adenoid cystic carcinoma, we developed a novel treatment combining gene therapy and nanotechnology. In this study, we created a plasmid, pACTERT-TRAIL, which used the human telomerase reverse transcriptase promoter, a tumor-specific promoter, to drive tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). A Fe3O4-PEI-plasmid complex (FPP) was generated, in which the iron oxide nanoparticles were modified by positively charged polyethylenimine (PEI) to enable them to carry the negatively charged plasmid. In vitro transfection assays showed that efficiency of magnetofection (i.e., FPP transfection) was sixfold higher compared to PEI alone or Lipofectamine 2000 (hereafter referred to as lipofectin) (P < 0.05). Importantly, apoptotic assays demonstrated that FPP-mediated TRAIL gene transfer could efficiently induce apoptosis of SACC-83 cells in vitro and in vivo. These results demonstrate that magnetofection of the plasmids driven by the tumor-specific promoter hTERT provides an effective way to deliver therapeutic genes for the treatment of adenoid cystic carcinoma in the future.From the Clinical EditorIn this novel study addressing adenoid cystic carcinoma, the authors created a plasmid to drive tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Following that, a Fe3O4-PEI-plasmid complex (FPP) was generated, in which the iron oxide nanoparticles were modified by positively charged polyethylenimine (PEI) enabling them to carry the negatively charged plasmid, giving rise to sixfold higher transfection rates compared to standard technology.

Graphical AbstractThis image shows SACC-83 cells transfected by the PEI modified Fe3O4 nanoparticles after 24 hours. The magnetic particle-DNA complexes are on the cell surface and in cytoplasm. The magnetic particle-DNA complex in the cytoplasm appears to have membrane-surrounded. This indicates that the PEI modified Fe3O4 nanoparticles can efficiently transfect the target cells.Figure optionsDownload high-quality image (95 K)Download as PowerPoint slide