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

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.