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Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging

Abstract

Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.

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Figure 1: Magnetism-engineered iron oxide (MEIO) nanoparticles and effects of their magnetic spin on MRI.
Figure 2: Size-dependent MR contrast effect of MnMEIO and MEIO nanoparticles.
Figure 3: Cytotoxicity test of MnMEIO nanoparticles and MnMEIO-Herceptin conjugates.
Figure 4: Evaluation of the MR sensitivity of MnMEIO-Herceptin conjugates for detection of the HER2/neu cancer marker, in comparison to that of CLIO-Herceptin conjugates and MEIO-Herceptin conjugates.
Figure 5: In vivo MR detection of cancer using magnetic nanoparticle–Herceptin conjugates.

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Acknowledgements

We would like to thank J.-S. Shin and K.-S. Kim for discussions, Y.-J. Kim for MR imaging, E.-S. Lee (Yonsei) and H.-J. Ko (Yonsei) for cell culture, J.-M. Oh (Chuncheon-Korea Basic Science Institute) for transmission electron microscopy (TEM), J.-g. Kim for high-voltage electron microscopic analyses, H.C. Kim for superconducting quantum interference device (SQUID) analyses, K.G. Cho for CLIO synthesis and J.D. Lee for the biodistribution study. This work was supported in part by the National Research Laboratory (M10600000255), National Cancer Institute Center for Cancer Nanotechnology Excellence, National Core Research Center (R15-2004-024-02002-0), the National R&D Program for Cancer Control of the Ministry of Health & Welfare (0320250-2), and the Korea Research Foundation (2004-003-E00171) and Second Stage of Brain Korea 21 of Chemistry and Medicine.

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Authors

Contributions

J.C., Y.-M.H. and J.-S.S. designed research. J.-H.L., J.-w.S., J.-t.J., H.-T.S., S.K. and E.-J.C. performed the experimental research. H.-G.Y. performed the receptor expression level analyses. Y.-w.J. and J.C. wrote the paper.

Corresponding authors

Correspondence to Jin-Suck Suh or Jinwoo Cheon.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Colloidal stability, structural characterization and size-dependent magnetism of MnMEIO nanoparticles. (PDF 586 kb)

Supplementary Fig. 2

Determination of HER2/neu expression levels of various cell lines by qRT-PCR analyses. (PDF 63 kb)

Supplementary Fig. 3

Determination of target-specificity of MnMEIO-Herceptin and CLIO-Herceptin conjugates. (PDF 99 kb)

Supplementary Fig. 4

Examination of passive targeting effects on MR signal. (PDF 418 kb)

Supplementary Fig. 5

Comparison of various nanoparticle-Herceptin conjugates in their in vivo MR cancer detection capability. (PDF 227 kb)

Supplementary Fig. 6

Column chromatography results of MnMEIO-Herceptin conjugates. (PDF 87 kb)

Supplementary Methods (PDF 91 kb)

Supplementary Note (PDF 131 kb)

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Lee, JH., Huh, YM., Jun, Yw. et al. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med 13, 95–99 (2007). https://doi.org/10.1038/nm1467

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