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In Vivo Detection of miRNA Expression in Tumors Using an Activatable Nanosensor

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Abstract

Purpose

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.

Procedures

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.

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Acknowledgments

The authors would like to acknowledge the National Institutes of Health (R01CA16346101A1 from the National Cancer Institute to ZM and 5T32CA009502 to AM) and the Breast Cancer Alliance (Young Investigator Award to ZM) for funding support.

Funding

The study was supported under grants R01CA16346101A1 from the National Cancer Institute to ZM, the Young Investigator Award by the Breast Cancer Alliance to ZM, and 5T32CA009502 to AM.

Author information

Authors and Affiliations

  1. Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA

    Byunghee Yoo, Amol Kavishwar, Alana Ross, Pamela Pantazopoulos, Anna Moore & Zdravka Medarova

  2. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA

    Anna Moore & Zdravka Medarova

Authors
  1. Byunghee Yoo
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  2. Amol Kavishwar
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  3. Alana Ross
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  4. Pamela Pantazopoulos
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  5. Anna Moore
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  6. Zdravka Medarova
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Corresponding authors

Correspondence to Anna Moore or Zdravka Medarova.

Electronic supplementary material

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ESM 1

Supplemental Figure 1. Relative fluorescence intensity in miR-10b active and miR-10b inhibited MDA-MB-231 tumors at a early time points after nanosensor injection (0–3 h) and b late time points after nanosensor injection (3–24 h). (PDF 435 kb)

Supplemental Figure 2. Relative fluorescence intensity in MDA-MB-231 and MCF-7 tumors at a early time points after nanosensor injection (0–3 h) and b. late time points after nanosensor injection (3–40 h).

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Yoo, B., Kavishwar, A., Ross, A. et al. In Vivo Detection of miRNA Expression in Tumors Using an Activatable Nanosensor. Mol Imaging Biol 18, 70–78 (2016). https://doi.org/10.1007/s11307-015-0863-3

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  • DOI: https://doi.org/10.1007/s11307-015-0863-3

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