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M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

Nature Nanotechnology volume 7, pages 677–682 (2012)Cite this article

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Abstract

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein–protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3,4,5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

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Figure 1: Schematic and targeting in vitro of M13-templated magnetic nanoparticles for MR imaging.
Figure 2: Material characterization of MNPs and M13-templated MNPs.
Figure 3: Targeting in vivo using MRI and correlative histology.
Figure 4: Amplified targeting in vitro.

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Acknowledgements

This work was supported by the NIH Center for Cancer Nanotechnology Excellence U54- CA151884 and NIH NCI RO1 CA137071. The authors thank J. Roy for assistance with MRI and F. Reynolds for excellent technical assistance. The authors thank M. Bevard for immunohistochemistry assistance and D. Pheasant and the Biophysical Instrumentation Facility for use of the DLS. The authors also thank Jennifer Hsieh with help with XRD. The authors acknowledge the Center for Materials Science and Engineering for the use of the ICP-AES and TEM and the Koch Institute Swanson Biotechnology Center for DNA sequencing.

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Authors and Affiliations

  1. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Debadyuti Ghosh, Youjin Lee, Aditya G. Kohli, Dong Soo Yun & Angela M. Belcher

  2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Debadyuti Ghosh & Angela M. Belcher

  3. Biomedical Engineering and Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, 22904, Virginia, USA

    Stephanie Thomas & Kimberly A. Kelly

  4. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Angela M. Belcher

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  1. Debadyuti Ghosh
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  5. Dong Soo Yun
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  7. Kimberly A. Kelly
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Contributions

D.G., K.A.K. and A.M.B. conceived and designed the experiments. D.G., Y.L. and S.T. performed experiments. D.G., Y.L., S.T. and A.G.K. contributed new reagents. D.S.Y. conducted high-resolution transmission electron microscopy. D.G. and K.A.K. analysed the data. D.G., K.A.K. and A.M.B. co-wrote the paper.

Corresponding authors

Correspondence to Angela M. Belcher or Kimberly A. Kelly.

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The authors declare no competing financial interests.

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Ghosh, D., Lee, Y., Thomas, S. et al. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer. Nature Nanotech 7, 677–682 (2012). https://doi.org/10.1038/nnano.2012.146

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