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Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration

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Tumor Biology

Abstract

The purpose of this study was to prepare tumor-specific dual-mode nanobubbles as both ultrasound contrast agents (UCAs) and near-infrared fluorescence (NIRF) imaging agents for female tumors. Recent studies have demonstrated the conjugation of anti-tumor ligands on the surface of nanobubbles for use as molecule-targeting ultrasound contrast agents for tumor visualization. However, this complicated procedure has also posed a challenge to nanobubble stability. Thus, in the present study, we combined the fluorescent dye, NIRF IR-780 iodide, which has lipid solubility and tumor-targeting characteristics, with the phospholipid film of nanobubbles that we constructed. We then characterized the physical features of the IR-780-nanobubbles, observed their tumor-targeting capacity in multiple female tumor cell types in vitro, and verified their capability for use in tumor-specific ultrasound contrast imaging and NIRF imaging in vivo. The results showed that the new IR-780-nanobubbles had a uniform nano-size (442.5 ± 48.6 nm) and stability and that they were safe and effective at NIRF imaging and ultrasound imaging in vitro. The IR-780-nanobubbles were found to automatically accumulate on different female tumor cells in vitro with a considerable targeting rate (close to 40 %) but did not accumulate on cardiac muscle cells used as a negative control. Importantly, the IR-780-nanobubbles can detect female tumors precisely via dual-mode imaging in vivo. In conclusion, the new dual-mode IR-780-nanobubbles are stable and have potential advantages in non-invasive tumor-specific detection for female tumors via contrast-enhanced ultrasound and NIRF imaging.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (grant number 81571730). The authors are grateful to the Department of Pharmaceutical Analysis and the Department of Molecular Biology, Fourth Military Medical University for their technical support and kind provision of equipment.

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    Authors and Affiliations

    1. Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an, China

      Hengli Yang, Tian Zhou, Wenbin Cai, Xi Liu, Yixiao Wang, Li Zhang & Yunyou Duan

    2. Department of Urology, PLA 105 Hospital, Hefei, China

      Xiaomin Yi

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    1. Hengli Yang
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    2. Tian Zhou
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    3. Wenbin Cai
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    4. Xiaomin Yi
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    5. Xi Liu
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    7. Li Zhang
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    Correspondence to Li Zhang or Yunyou Duan.

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    Hengli Yang and Tian Zhou contributed equally to this work.

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    Yang, H., Zhou, T., Cai, W. et al. Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration. Tumor Biol. 37, 14153–14163 (2016). https://doi.org/10.1007/s13277-016-5238-0

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    • DOI: https://doi.org/10.1007/s13277-016-5238-0

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