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Surveillance nanotechnology for multi-organ cancer metastases

Abstract

The identification and molecular profiling of early metastases remains a major challenge in cancer diagnostics and therapy. Most in vivo imaging methods fail to detect small cancerous lesions, a problem that is compounded by the distinct physical and biological barriers associated with different metastatic niches. Here, we show that intravenously injected rare-earth-doped albumin-encapsulated nanoparticles emitting short-wave infrared light (SWIR) can detect targeted metastatic lesions in vivo, allowing for the longitudinal tracking of multi-organ metastases. In a murine model of human breast cancer, the nanoprobes enabled whole-body SWIR detection of adrenal-gland microlesions and bone lesions that were undetectable via contrast-enhanced magnetic resonance imaging as early as three and five weeks post-inoculation, respectively. Whole-body SWIR imaging of nanoprobes functionalized to differentially target distinct metastatic sites and administered to a biomimetic murine model of human breast cancer resolved multi-organ metastases that showed varied molecular profiles in the lungs, adrenal glands and bones. Real-time surveillance of lesions in multiple organs should facilitate pre- and post-therapy monitoring in preclinical settings.

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The authors declare no competing financial interests.

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Acknowledgements

We are grateful for access to the Rutgers Molecular Imaging Core (D. Adler), Analytical Core at the Environmental and Occupational Health Sciences Institute, Rutgers University (B. Buckley and E. McCandish), and for funding from the National Institutes of Health National Institute of Biomedical Imaging and Bioengineering (EB018378-01 and EB015169-02), Singapore University of Technology and Design-Massachusetts Institute of Technology International Design Centre (project number IDG31400106), and the Singapore Ministry of Education (project number MOE2014-T2-2-145). We also thank Y. Kang of Princeton University for the SCP28, SCP2 and 4175-TR cells. We acknowledge Malvern Instruments for providing the equipment used for the DLS measurements.

Author information

H.K., M.Z., V.G., S.G., C.M.R. and P.V.M. conceived the study and designed the experiments. H.K., V.G., M.Z., W.B-P., M.J.D. and S.R.B performed the animal experiments. H.K., M.Z. and M.J.D. performed in vitro experiments. M-C.T., X.Z., Y.S. and R.E.R. designed and fabricated the rare-earth nanoparticles. H.K., M.Z., L.H.M., L.M.H., V.G. and M.C.P. analysed the data. H.K., M.Z., M-C.T., C.M.R., M.C.P., V.G. and P.V.M. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Correspondence to Mark C. Pierce or Vidya Ganapathy or Prabhas V. Moghe.

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Supplementary Information

Supplementary figures and video captions.

Life Sciences Reporting Summary.

Supplementary Video 1

Real-time short-wave-infrared-light imaging of athymic nude mice in supine position intravenously injected with 200 μl of rare-earth albumin nanocomposites.

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Further reading

Fig. 1: Design and workflow of photonic nanotechnology for cancer-metastasis detection and profiling.
Fig. 2: SWIR imaging of photonic nanoparticles discerns bone lesions in vivo that are undetectable by conventional MRI and CT.
Fig. 3: Distal bone lesions can be detected with SWIR imaging earlier than with MRI and CT in a biomimetic metastasis model.
Fig. 4: Differential niche-based accumulation of ReANC and fReANC formulations leads to multi-organ detection of metastases in a luminal breast cancer model.
Fig. 5: Passive accumulation of ReANCs, via the discontinuous fenestration architecture of bone tissue, in a metastatic luminal breast cancer model.
Fig. 6: Differential accumulation of ReANCs in leg lesions and fReANCs in lung lesions in a multi-organ metastatic model.
Fig. 7: Distal bone lesions can be detected with SWIR imaging earlier than with contrast-enhanced MRI in a biomimetic metastasis model.