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A hepatocellular carcinoma–bone metastasis-on-a-chip model for studying thymoquinone-loaded anticancer nanoparticles

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Abstract

We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma (HCC)–bone metastasis and to analyze the inhibitory effect of an herb-based compound, thymoquinone (TQ), in hindering the migration of liver cancer cells into the bone compartment. The bioreactor consisted of two chambers, one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite (HAp). Above these chambers, a microporous membrane was placed to resemble the vascular barrier, where medium was circulated over the membrane. It was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone chamber. The number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the hydrogel. TQ was then used as a metastasis-controlling agent in both free form and encapsulated nanoparticles, to analyze its suppressing effect on HCC metastasis. Results indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory effect. In summary, HCC–bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process, hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.

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Availability of data and material (data transparency)

The datasets that support the findings of this study are available from the corresponding authors upon reasonable request. All requests for raw and analyzed data and materials will be promptly reviewed by the Brigham and Women’s Hospital to verify whether the request is subject to any intellectual property or confidentiality obligations. Any data and materials that can be shared will be released via a Material Transfer Agreement.

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Funding

This work was supported by the National Institutes of Health (K99CA201603, R00CA201603, R21EB025270, R21EB026175, R01EB028143), the New England Anti-Vivisection Society, and the Brigham Research Institute.

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Authors and Affiliations

  1. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA

    Fatemeh Sharifi, Ozlem Yesil-Celiktas, Sushila Maharjan, Saghi Saghazadeh & Yu Shrike Zhang

  2. School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran

    Fatemeh Sharifi, Keikhosrow Firoozbakhsh & Bahar Firoozabadi

  3. Department of Bioengineering, Faculty of Engineering, Ege University, Bernova, Izmir, Turkey

    Ozlem Yesil-Celiktas & Aslihan Kazan

Authors
  1. Fatemeh Sharifi
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  2. Ozlem Yesil-Celiktas
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  3. Aslihan Kazan
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  4. Sushila Maharjan
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  5. Saghi Saghazadeh
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  6. Keikhosrow Firoozbakhsh
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  7. Bahar Firoozabadi
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  8. Yu Shrike Zhang
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Corresponding authors

Correspondence to Bahar Firoozabadi or Yu Shrike Zhang.

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Sharifi, F., Yesil-Celiktas, O., Kazan, A. et al. A hepatocellular carcinoma–bone metastasis-on-a-chip model for studying thymoquinone-loaded anticancer nanoparticles. Bio-des. Manuf. 3, 189–202 (2020). https://doi.org/10.1007/s42242-020-00074-8

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  • DOI: https://doi.org/10.1007/s42242-020-00074-8

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