title: Superparamagnetic iron oxide nanoparticles mediated (131)I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF).
  
  
  METHODS
  hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment.
  
  
  RESULTS
  131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control.
  
  
  CONCLUSIONS
  EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Liangqian
authors.initials: L
authors.lastname: Tong
authors.forename: Jiansha
authors.initials: J
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Han
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. xwbio2013@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D005290:Ferric Compounds / Q000008:administration & dosage*; D056945:Hep G2 Cells; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D055909:Magnetic Field Therapy / Q000379:methods; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D005290:Ferric Compounds; D007457:Iodine Radioisotopes; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide