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Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide nanoparticles

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Abstract

Objective

Using RGD10–NGR9 dual-targeting superparamagnetic iron oxide nanoparticles to evaluate their potential value in tumor angiogenesis magnetic resonance imaging (MRI) and the biodistribution in vitro and in vivo.

Materials and methods

Dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were designed and synthesized in our previous study. In vitro, prussian blue staining and phenanthroline colorimetry were conducted to evaluate binding affinity and adsorption of dual-targeting USPIO nanoparticles to αvβ3-integrin/APN positive cells. In vivo, a xenograft mouse tumor model was used to evaluate the potential of the dual-targeting nanoparticles as an MRI contrast agent. After intravenous injection, the contrast-to-noise ratio (CNR) values of MR images obtained were calculated at predetermined time-points. The iron level was detected to access the biodistribution and plasma half-time.

Results

In vitro, dual-targeting USPIO nanoparticles bound to proliferating human umbilical vein endothelia cells with high specificity. In vivo, contrast MRI of xenograft mice using dual-targeting nanoparticles demonstrated a significant decrease in signal intensity and a greater increase in CNR than standard MRI and facilitated the imaging of tumor angiogenesis in T2*WI. In terms of biodistribution, dual-targeting USPIO nanoparticles increased to 1.83 times in tumor lesions as compared to the control. And the plasma half-time was about 6.2 h.

Conclusion

A novel RGD10–NGR9 dual-targeting USPIO has a great potential value as a contrast agent for the identification of tumor angiogenesis on MRI, according to the high specific affinity in vitro and in vivo.

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Acknowledgements

This work was supported by the Science and Technology Commission of Shanghai Municipality (No. 14411966400, 15ZR1434500), National Natural Science Foundation of China (No. 81572269).

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Author notes

  1. T. Wu and X. Ding have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    T. Wu, A. K. Soodeen-Lalloo & J.-Y. Shi

  2. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    X. Ding & B. Su

  3. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    L. Zhang

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  1. T. Wu
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  2. X. Ding
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  3. B. Su
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  4. A. K. Soodeen-Lalloo
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  5. L. Zhang
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  6. J.-Y. Shi
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Corresponding authors

Correspondence to L. Zhang or J.-Y. Shi.

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The authors indicate no potential conflicts of interest.

Ethical approval

The animal study was conducted in accordance with the Institutional Animal Care and Use Committee (IACUC) guidelines and was under approval of Tongji University Animal Center.

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Wu, T., Ding, X., Su, B. et al. Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide nanoparticles. Clin Transl Oncol 20, 599–606 (2018). https://doi.org/10.1007/s12094-017-1753-8

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  • DOI: https://doi.org/10.1007/s12094-017-1753-8

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