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Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of VEGFR2-targeted CD-TK-loaded cationic nanobubbles in the treatment of bladder cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

The CD-TK double suicide gene has become an effective therapy for bladder cancer. A novel molecular-targeted ultrasound (US) method has been developed to precisely guide nanobubbles loaded with this gene to regions within bladder tumor cells and is widely used due to its efficiency in delivering drugs to the target tumor.

Methods

Uniform nanoscaled nanobubbles loaded with CD-TK double suicide gene were developed using a thin-film hydration sonication, carbodiimide chemistry approaches, and electrostatic adsorption methods.

Results

In the present study, we synthesized CD-TK double suicide gene-loaded cationic nanobubbles conjugated with anti-VEGFR2 that can bind with VEGFR2-positive cells. Fluorescence and flow cytometry evidence show that CD-TK double suicide gene-loaded nanobubbles were successfully developed. CD-TK-CNBs delivered via US-mediated nanobubble destruction (UMND) enhanced transfection efficiency, overexpression of CD-TK double suicide gene, and tumor cell apoptosis, and inhibited tumor cell growth in vitro.

Conclusions

These CD-TK-CNBs may become a novel treatment for bladder cancer.

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Availability of data and materials

Materials are available upon request.

Abbreviations

UMND:

Ultrasound-mediated nanobubble destruction

CD:

Cytosine deaminase

US:

Ultrasound

5-FC:

5-Fluorine cytosine

TK:

Thymine kinase gene

GCV:

Ganciclovir

DPPC:

1,2-Dipalmitoyl-sn-glycero-3-phosphocholine

(DSPE-PEG 2000)-COOH:

Carboxyl-modified1,2-distearoyl-sn-glycero-3-phosphoetha-nolamine

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Acknowledgements

This study was approved by The Animal Ethics Committee of Chongqing Medical University and the ARRIVE guidelines followed for the welfare of the animals.

Funding

The present work was sponsored by the National Science Foundation of China No. 81650003, Research on the Frontiers and Application of Chongqing Science and Technology Commission No. cstc2015jcyjA10030, Key Medical Scientific Research Project of Chongqing Municipal Health department No. 2012-1-037, and the Science and Technology Project of Chongqing Yuzhong District No. 20130117, Project of Science and Technology Innovation Foundation of Zhongnan Hospital of Wuhan University No. znpy2018021.

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Authors and Affiliations

  1. Department of Intensive Care Unit, Zhuhai People’s Hospital (Zhuhai hospital affiliated with Jinan University), Zhuhai, 519000, China

    Cong Hu

  2. Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, No. 76, Linjiang Road, Yuzhong District, Chongqing, 400010, China

    Depeng Jiang & Jing Wang

  3. Department of Ultrasound, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Meng Wu

  4. Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, No. 76, Linjiang Road, Yuzhong District, Chongqing, 400010, China

    Ronggui Zhang

Authors
  1. Cong Hu
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  2. Depeng Jiang
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  3. Meng Wu
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  4. Jing Wang
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  5. Ronggui Zhang
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Contributions

CH and RG Z conceived of and designed the study. CH, MW, JW, and DP J performed the experiments. CH, JW, and RG Z analyzed and interpreted the data. CH wrote the manuscript. RG Z and JW revised the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ronggui Zhang.

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Hu, C., Jiang, D., Wu, M. et al. Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of VEGFR2-targeted CD-TK-loaded cationic nanobubbles in the treatment of bladder cancer. J Cancer Res Clin Oncol 146, 1415–1426 (2020). https://doi.org/10.1007/s00432-020-03160-7

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  • DOI: https://doi.org/10.1007/s00432-020-03160-7

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