title: In Vivo Detection of miRNA Expression in Tumors Using an Activatable Nanosensor.
abstract: OBJECTIVE
  The development of tools for the analysis of microRNA (miRNA) function in tumors can advance our diagnostic and prognostic capabilities. Here, we describe the development of technology for the profiling of miRNA expression in the tumors of live animals.
  
  
  METHODS
  The approach is based on miRNA nanosensors consisting of sensor oligonucleotides conjugated to magnetic nanoparticles for systemic delivery. Feasibility was demonstrated for the detection of miR-10b, implicated in epithelial to mesenchymal transition and the development of metastasis. The miR-10b nanosensor was tested in vivo in two mouse models of cancer. In the first model, mice were implanted subcutaneously with MDA-MB-231-luc-D3H2LN tumors, in which miR-10b was inhibited. In the second model, mice were implanted bilaterally with metastatic MDA-MB-231 and nonmetastatic MCF-7 cells. The nanosensors were injected intravenously, and fluorescence intensity in the tumors was monitored over time.
  
  
  RESULTS
  We showed that the described nanosensors are capable of discriminating between tumors based on their expression of miR-10b. Radiant efficiency was higher in the miR-10b-active tumors than in the miR-10b-inhibited tumors and in the MDA-MB-231 tumors relative to the MCF-7 tumors.
  
  
  CONCLUSIONS
  The described technology provides an important tool that could be used to answer questions about microRNA function in cancer.
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
authors.forename: Byunghee
authors.initials: B
authors.lastname: Yoo
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
authors.forename: Amol
authors.initials: A
authors.lastname: Kavishwar
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
authors.forename: Alana
authors.initials: A
authors.lastname: Ross
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Pantazopoulos
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. amoore@helix.mgh.harvard.edu.|Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. amoore@helix.mgh.harvard.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. zmedarova@mgh.harvard.edu.|Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. zmedarova@mgh.harvard.edu.
authors.forename: Zdravka
authors.initials: Z
authors.lastname: Medarova
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics*; D009841:Oligonucleotides / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides
keywords: Activatable probes; Cancer; Fluorescence; Magnetic nanoparticles; Metastasis; Nanosensors; Oligonucleotides; miRNA