title: Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer.
abstract: OBJECTIVE
  Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.
  
  
  METHODS
  Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.
  
  
  RESULTS
  800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM(-1)·s(-1). Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.
  
  
  CONCLUSIONS
  This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.
authors: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Pu
authors: P
authors: Wang
authors: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Yazhuo
authors: Y
authors: Qu
authors: Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Chuan
authors: C
authors: Li
authors: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Li
authors: L
authors: Yin
authors: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Caifei
authors: C
authors: Shen
authors: Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Wei
authors: W
authors: Chen
authors: Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Shiming
authors: S
authors: Yang
authors: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Xiuwu
authors: X
authors: Bian
authors: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Dianchun
authors: D
authors: Fang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D051929:CD146 Antigen / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D051929:CD146 Antigen; D012822:Silicon Dioxide
keywords: EMT; SPION; SPION@dSiO2; gastric cancer; nanotechnology; xenograft
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