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.

中文翻译：

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肝细胞癌骨转移的芯片模型研究负载胸腺醌的抗癌纳米颗粒

我们报告了一个转移芯片平台的开发，该平台可用于建模和跟踪肝细胞癌（HCC）–骨转移，并分析基于草药的化合物胸腺醌（TQ）在抑制肝脏迁移中的抑制作用癌细胞进入骨腔。该生物反应器由两个小室组成，一个小室可容纳封装的HepG2细胞，另一个小室可容纳羟基磷灰石（HAp）。在这些腔室上方，放置了微孔膜以类似于血管屏障，其中介质在膜上循环。观察到肝癌细胞在肿瘤微组织内增殖，并从HCC腔室扩散到循环流，并最终进入骨腔。在水凝胶中存在HAp的情况下，转移至骨腔的HepG2细胞数量明显增加。然后将TQ用作游离形式和包封的纳米颗粒的转移控制剂，以分析其对HCC转移的抑制作用。结果表明，纳米颗粒包封的TQ提供了更长的抑制作用时间。总之，HCC骨上单芯片转移平台已被证明可以模拟癌症转移过程的某些关键方面，从而证实了开展与转移相关的生物学研究以及改进抗转移药物筛选的潜力。结果表明，纳米颗粒包封的TQ提供了更长的抑制作用时间。总之，HCC骨上单芯片转移平台已被证明可以模拟癌症转移过程的某些关键方面，从而证实了开展与转移相关的生物学研究以及改进抗转移药物筛选的潜力。结果表明，纳米颗粒包封的TQ提供了更长的抑制作用时间。总之，HCC骨上单芯片转移平台已被证明可以模拟癌症转移过程的某些关键方面，从而证实了开展与转移相关的生物学研究以及改进抗转移药物筛选的潜力。