Peishan Teo1, Xiaowen Wang2, Benke Chen1,3, Han Zhang1,4, Xin Yang1,3, Yun Huang1, Jintian Tang1. 1. 1 Key Laboratory of Particle & Radiation Imaging of Ministry of Education, Department of Engineering Physics, Tsinghua University , Beijing, People's Republic of China . 2. 2 Yuquan Hospital, Medical Center, Tsinghua University , Beijing, People's Republic of China . 3. 3 Department of Biological Pharmaceuticals, Beijing University of Chinese Medicine , Beijing, People's Republic of China . 4. 4 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University , Jinan, People's Republic of China .
Abstract
BACKGROUND: Magnetic nanoparticles are increasingly applied in clinical area for drug delivery, also in magnetic induction hyperthermia (MIH), and so on. The present research would prepare appropriately modified superparamagnetic iron oxide nanoparticles (SPIONs) to conduct MIH and transfect the anticancer cytokine TNF-α into cells. MATERIALS AND METHODS: The SPIONs were surface-modified by 3-aminopropyltriethoxysilane (APTS) and/or protamine sulfate (PRO). The combined MIH using SPIONs and gene therapy were applied to treat Hep G2 cells and tumor model transplanted in nude mice. RESULTS: The PRO-SPIONs (the surfaces were sequentially modified by APTS and PRO) showed high transfection efficiency for TNF-α gene with no obvious cytotoxicity. It also exhibited great temperature rising performance under alternating current magnetic field. The combined MIH and gene therapy using PRO-SPIONs/TNF-α complex could reduce cell variability of Hep G2 cells and tumor size transplanted in nude mice. CONCLUSIONS: The PRO-SPIONs efficiently transfect the TNF-α gene into Hep G2 cells. Cells expressed more TNF-α when they were exposed to alternating current magnetic field only once. Combined MIH and gene therapy for treatment in vivo exhibited better effects than MIH or gene therapy alone. The combined MIH and gene therapy is promising in liver cancer treatment.
BACKGROUND: Magnetic nanoparticles are increasingly applied in clinical area for drug delivery, also in magnetic induction hyperthermia (MIH), and so on. The present research would prepare appropriately modified superparamagnetic iron oxide nanoparticles (SPIONs) to conduct MIH and transfect the anticancer cytokine TNF-α into cells. MATERIALS AND METHODS: The SPIONs were surface-modified by 3-aminopropyltriethoxysilane (APTS) and/or protamine sulfate (PRO). The combined MIH using SPIONs and gene therapy were applied to treat Hep G2 cells and tumor model transplanted in nude mice. RESULTS: The PRO-SPIONs (the surfaces were sequentially modified by APTS and PRO) showed high transfection efficiency for TNF-α gene with no obvious cytotoxicity. It also exhibited great temperature rising performance under alternating current magnetic field. The combined MIH and gene therapy using PRO-SPIONs/TNF-α complex could reduce cell variability of Hep G2 cells and tumor size transplanted in nude mice. CONCLUSIONS: The PRO-SPIONs efficiently transfect the TNF-α gene into Hep G2 cells. Cells expressed more TNF-α when they were exposed to alternating current magnetic field only once. Combined MIH and gene therapy for treatment in vivo exhibited better effects than MIH or gene therapy alone. The combined MIH and gene therapy is promising in liver cancer treatment.
Entities:
Keywords:
TNF-α; gene therapy; magnetic induction hyperthermia; superparamagnetic iron oxide nanoparticles