Citation: Weifei Zhang, Danfeng Xu, Jinru Tian, Ying Kan, Xuanlin Feng, Jia Liu, Hongmei Li, Nan Li. An inverse opal structure-based human alveolar lung-on-a-chip for the study of Osimertinib treatment in non-small cell lung cancer[J]. Chinese Chemical Letters, ;2026, 37(4): 111453. doi: 10.1016/j.cclet.2025.111453 shu

An inverse opal structure-based human alveolar lung-on-a-chip for the study of Osimertinib treatment in non-small cell lung cancer

Weifei Zhang ^a ,
Danfeng Xu ^a ,
Jinru Tian ^b ,
Ying Kan ^a ,
Xuanlin Feng ^a ,
Jia Liu ^a ,
Hongmei Li ^{a, c, *,} ,
Nan Li ^{b, *,}

a.
Key Laboratory of Chemical Metrology and Applications on Nutrition and Health, State Administration for Market Regulation, Division of Chemical Metroloy and Analytical Science, National Institute of Metrology, Beijing 100029, China
b.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
c.
State Key Laboratory of Green Biomanufacturing College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China

lihm@buct.edu.cn

linan@bucm.edu.cn

Received Date: 6 March 2025
Revised Date: 12 June 2025
Accepted Date: 12 June 2025
Available Online: 13 June 2025

Figures(5)

The deficiency of reliable and physiologically relevant distal lung models has been regarded as a crucial issue for drug research on non small cell lung cancer (NSCLC). In this study, an inverse opal structure-based lung-on-a-chip was established to replicate the geometric dimensions and topography of the native lung alveoli, and two lateral microchambers were designed to induce pressure-driven stretching for the simulation of respiratory movement. Further, a concentration gradient generator was applied to connect with lung-on-a-chip for the creation of different enzyme environments to mimic the individual variability of P450s enzymes in lung patients. Based on this microfluidic platform, the Osimertinib implications in NSLC was investigated from the aspect of metabolism and adapted resistance. The results suggested that Osimertinib exhibited discernible difference in metabolism under diverse enzyme condition. Additionally, in contrast with the control group, all groups with Osimertinib treatment triggered the alterations of amino acid metabolisms and energy supply, indicating that targeting energy supply process might be an effective measure to prevent tumor cells from generating drug resistance.
- Lung-on-a-chip,
- Inverse opal structure,
- Concentration gradient generator,
- Osimertinib metabolism,
- Adapted resistance,
- Amino acid metabolism
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