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Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness

Nature Nanotechnologyvolume 14pages279286 (2019) | Download Citation


While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surrounding vasculature and subsequently extravasation, accelerating metastasis. Here, we show that nanoparticles induce endothelial leakiness through disruption of the VE-cadherin–VE-cadherin homophilic interactions at the adherens junction. We show that intravenously injected titanium dioxide, silica and gold nanoparticles significantly accelerate both intravasation and extravasation of breast cancer cells in animal models, increasing the extent of existing metastasis and promoting the appearance of new metastatic sites. Our results add to the understanding of the behaviour of nanoparticles in complex biological systems. The potential for NanoEL needs to be taken into consideration when designing future nanomedicines, especially nanomedicine to treat cancer.

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The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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This work was supported by Ministry of Education Academic Research Grants (R-279–000–418–112, R-279-000-498-114 and R148–000–217–112).

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Author notes

  1. These authors contributed equally: Fei Peng, Magdiel Inggrid Setyawati, Jie Kai Tee.


  1. Department of Chemical and Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore

    • Fei Peng
    • , Magdiel Inggrid Setyawati
    • , Jie Kai Tee
    • , Xianguang Ding
    • , Jinping Wang
    •  & David Tai Leong
  2. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore

    • Fei Peng
    • , Jie Kai Tee
    •  & Han Kiat Ho
  3. NUS Graduate School for Integrative Sciences & Engineering, Singapore, Singapore

    • Jie Kai Tee
    • , Han Kiat Ho
    •  & David Tai Leong
  4. Department of Pathology, National University Hospital and National University of Singapore, Singapore, Singapore

    • Min En Nga


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D.T.L. and H.K.H. conceived the hypotheses, designed the experiments, performed the analysis and interpretations, and wrote the paper. F.P., M.I.S. and J.K.T. designed and performed the experiments, analysed the results and wrote the paper. X.D. and J.P.W. performed the experiments. M.E.N. analysed the results.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Han Kiat Ho or David Tai Leong.

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