Glioma is one of the most aggressive and highly fatal diseases with an extremely poor prognosis. Considering the poor clinical response to therapy in glioma, it is urgent to establish an in vitro model to facilitate the screening and assessment of anti-brain-tumor drugs. The blood-brain barrier (BBB), as well as liver metabolism plays an important role in determining the pharmacological activity of many anti-brain-tumor drugs. In this work, we designed a multi-interface liver-brain chip integrating co-culture system to assess hepatic metabolism dependent cytotoxicity of anti-brain-tumor drug in vitro. This microdevice composed of three microchannels which were separated by porous membrane and collagen. HepG2 and U87 cells were cultured in separated channels as mimics of liver and glioblastoma. Brain microvascular endothelial cells (BMECS) and cerebral astrocytes were co-cultured on collagen to mimic the brain microvascular endothelial barrier. Three common anti-tumor drugs, paclitaxel (PTX), capecitabine (CAP) and temozolomide (TMZ), were evaluated on this chip. In integrated liver-brain chip, liver enhanced the cytotoxicity of CAP on U87 cells by 30%, but having no significant effect on TMZ. The BBB decreased the cytotoxicity of PTX by 20%, while no significant effects were observed on TMZ and CAP, indicating the importance of liver metabolism and blood-brain barrier on the evaluation of anti-brain-tumor drugs. This work provides a biomimetic liver-brain model to mimic the physiological and pharmacological processes in vitro and presents a simple platform for long-term cell co-culture, drug delivery and metabolism, and real-time analysis of drug effects on brain cancer.

中文翻译：

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肝脑芯片评估胶质母细胞瘤的肝脏药物代谢

神经胶质瘤是最具侵袭性和高度致命的疾病之一，预后极差。考虑到胶质瘤治疗的临床反应较差，迫切需要建立体外模型以促进抗脑肿瘤药物的筛选和评估。血脑屏障 (BBB) 以及肝脏代谢在决定许多抗脑肿瘤药物的药理活性方面起着重要作用。在这项工作中，我们设计了一种集成共培养系统的多界面肝脑芯片，以在体外评估抗脑肿瘤药物的肝脏代谢依赖性细胞毒性。该微型装置由三个微通道组成，由多孔膜和胶原蛋白隔开。HepG2 和 U87 细胞在分离的通道中培养，作为肝脏和胶质母细胞瘤的模拟物。脑微血管内皮细胞 (BMECS) 和脑星形胶质细胞在胶原蛋白上共培养以模拟脑微血管内皮屏障。在该芯片上评估了三种常见的抗肿瘤药物，紫杉醇 (PTX)、卡培他滨 (CAP) 和替莫唑胺 (TMZ)。在集成的肝脑芯片中，肝脏使CAP对U87细胞的细胞毒性提高了30%，但对TMZ没有显着影响。BBB 使 PTX 的细胞毒性降低了 20%，而对 TMZ 和 CAP 没有观察到显着影响，表明肝脏代谢和血脑屏障在抗脑肿瘤药物评价中的重要性。这项工作提供了一个仿生肝脑模型来模拟体外生理和药理过程，并为长期细胞共培养、药物递送和代谢提供了一个简单的平台，