Li Wei, Sun Xindi, Ji Bing, Yang Xingyuan, Zhou Bingpu, Lu Zhanjun, Gao Xinghua
Materials Genome Institute, Shanghai University, Shanghai 200444, China.
Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Taipa, Macau 999078, China.
Micromachines (Basel). 2020 Nov 28;11(12):1054. doi: 10.3390/mi11121054.
Lung-on-a-chip devices could provide new strategies for a biomimetic lung cell microenvironment and construction of lung disease models in vitro, and are expected to greatly promote the development of drug evaluation, toxicological detection, and disease model building. In this study, we developed a novel poly (lactic-co-glycolic acid) (PLGA) nanofiber/polydimethylsiloxane (PDMS) microporous composite membrane-sandwiched lung-on-a-chip to perform anti-tumor drug testing. The composite membrane was characterized, and the results showed that it was permeable to molecules and thus could be used to study small-molecule drug diffusion. In addition, the microchip could apply perfusion fluids to simulate blood flow under extremely low fluid shear stress, and could also simulate the spherical-like shape of the alveoli by deformation of the composite membrane. Using this chip, we evaluated the anti-tumor drug efficacy of gefitinib in two kinds of non-small cell lung cancer cells, the lung adenocarcinoma NCI-H1650 cell line and the large cell lung cancer NCI-H460 cell line. We further probed the resistance of NCI-H460 cells to gefitinib under normoxic and hypoxic conditions. The established composite membrane-sandwiched lung chip can simulate more biochemical and biophysical factors in the lung physiological and pathological microenvironment, and it has important applications in the personalized treatment of lung tumors. It is expected to play a potential role in clinical diagnosis and drug screening.
肺芯片装置可为体外构建仿生肺细胞微环境和肺病模型提供新策略，有望极大地推动药物评价、毒理学检测及疾病模型构建的发展。在本研究中，我们开发了一种新型的聚乳酸-羟基乙酸共聚物（PLGA）纳米纤维/聚二甲基硅氧烷（PDMS）微孔复合膜夹心式肺芯片，用于进行抗肿瘤药物测试。对该复合膜进行了表征，结果表明它对分子具有通透性，因此可用于研究小分子药物扩散。此外，该微芯片能够施加灌注液以在极低的流体剪切应力下模拟血流，还能通过复合膜的变形模拟肺泡的球状形态。利用该芯片，我们评估了吉非替尼对两种非小细胞肺癌细胞，即肺腺癌NCI-H1650细胞系和大细胞肺癌NCI-H460细胞系的抗肿瘤药物疗效。我们进一步探究了NCI-H460细胞在常氧和低氧条件下对吉非替尼的耐药性。所构建的复合膜夹心式肺芯片能够模拟肺生理和病理微环境中的更多生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要应用。有望在临床诊断和药物筛选中发挥潜在作用。
