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 Fe(3)O(4)-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.


BACKGROUND
In 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 Fe(3)O(4)-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.
School of Stomatology, Jilin University, Changchun, China; State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, China.
Leiying
L
Miao
Kai
K
Zhang
Chunyan
C
Qiao
Xiangyu
X
Jin
Changyu
C
Zheng
Bai
B
Yang
Hongchen
H
Sun
D017209:Apoptosis; D003528:Carcinoma, Adenoid Cystic / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D008280:Magnetics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D017550:Spectroscopy, Fourier Transform Infrared; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human