Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells
Abstract In cancer cells, higher reactive oxygen species (ROS) than normal cells were observed due to hypermetabolism. The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity. By manipulating oxidation and antioxidant systems, chemotherapeutic drugs can selectively k...
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| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Microsystems & Nanoengineering |
| Online Access: | https://doi.org/10.1038/s41378-025-01016-z |
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| author | Yuxuan Zhu Zhichao Huang Shichao Tian Qi Wang Fan Wu Jingwen Liu Ping Wang Hao Wan Liujing Zhuang Deming Jiang |
| author_facet | Yuxuan Zhu Zhichao Huang Shichao Tian Qi Wang Fan Wu Jingwen Liu Ping Wang Hao Wan Liujing Zhuang Deming Jiang |
| author_sort | Yuxuan Zhu |
| collection | DOAJ |
| description | Abstract In cancer cells, higher reactive oxygen species (ROS) than normal cells were observed due to hypermetabolism. The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity. By manipulating oxidation and antioxidant systems, chemotherapeutic drugs can selectively kill cancer cells without hurting normal cells. As three-dimensional (3D) in vitro models, such as spheroids and organoids, have become widely used in cancer research, traditional detection methods (e.g., absorption tests or titration) are inadequate for detecting in 3D environments. Thus, it is crucial to find a new method to detect oxidative stress of 3D in vitro cancer models. Here, a nanocomposite electrochemical biosensor was exploited to evaluate oxidative stress of cancer cells cultured in the 3D environment. The oxidation-regulatory capacity of honokiol, a Magnolia genus-derived anti-cancer molecule, was evaluated. A screen-printed electrode (SPCE) was modified with reduced graphene oxide (RGO) and platinum nanoparticles (Pt NPs) to get Pt NPs/RGO/SPCE. Then the gelatin methacrylate/reduced graphene oxide (GelMA/RGO) hydrogel was applied to immobilized NCI-H1975 in a 3D bionic environment to get NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE. After optimizing the experiment condition, the Pt NPs/RGO/SPCE showed a detection threshold of 0.65 μM and a linear field from 1 to 10 μM for H2O2 detection while the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE sensitively responded to H2O2-induced oxidative stress. By utilizing the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE we found honokiol (a natural polyphenol constituent) inhibits NCI-H1975 by inducing oxidative stress. This simple cell-based electrochemical biosensor can in situ evaluate oxidative stress of 3D cancer models conveniently. It can also be easily extended to the study of the mechanism of action of other drugs and holds broad application prospects in the fields of new drug development and drug repurposing. |
| format | Article |
| id | doaj-art-bf466606bf3849e4be7b4a1d073bbf27 |
| institution | Kabale University |
| issn | 2055-7434 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Microsystems & Nanoengineering |
| spelling | doaj-art-bf466606bf3849e4be7b4a1d073bbf272025-08-20T03:45:49ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342025-08-0111111210.1038/s41378-025-01016-zNanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cellsYuxuan Zhu0Zhichao Huang1Shichao Tian2Qi Wang3Fan Wu4Jingwen Liu5Ping Wang6Hao Wan7Liujing Zhuang8Deming Jiang9Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityCenter of Clinical Big Data and Analytics of the Second Affiliated Hospital and School of Public Health, Zhejiang University School of MedicineBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityDepartment of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang UniversityAbstract In cancer cells, higher reactive oxygen species (ROS) than normal cells were observed due to hypermetabolism. The redox balance in cancer cells relies on accordingly upregulated antioxidant capacity. By manipulating oxidation and antioxidant systems, chemotherapeutic drugs can selectively kill cancer cells without hurting normal cells. As three-dimensional (3D) in vitro models, such as spheroids and organoids, have become widely used in cancer research, traditional detection methods (e.g., absorption tests or titration) are inadequate for detecting in 3D environments. Thus, it is crucial to find a new method to detect oxidative stress of 3D in vitro cancer models. Here, a nanocomposite electrochemical biosensor was exploited to evaluate oxidative stress of cancer cells cultured in the 3D environment. The oxidation-regulatory capacity of honokiol, a Magnolia genus-derived anti-cancer molecule, was evaluated. A screen-printed electrode (SPCE) was modified with reduced graphene oxide (RGO) and platinum nanoparticles (Pt NPs) to get Pt NPs/RGO/SPCE. Then the gelatin methacrylate/reduced graphene oxide (GelMA/RGO) hydrogel was applied to immobilized NCI-H1975 in a 3D bionic environment to get NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE. After optimizing the experiment condition, the Pt NPs/RGO/SPCE showed a detection threshold of 0.65 μM and a linear field from 1 to 10 μM for H2O2 detection while the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE sensitively responded to H2O2-induced oxidative stress. By utilizing the NCI-H1975/GelMA/RGO/Pt NPs/RGO/SPCE we found honokiol (a natural polyphenol constituent) inhibits NCI-H1975 by inducing oxidative stress. This simple cell-based electrochemical biosensor can in situ evaluate oxidative stress of 3D cancer models conveniently. It can also be easily extended to the study of the mechanism of action of other drugs and holds broad application prospects in the fields of new drug development and drug repurposing.https://doi.org/10.1038/s41378-025-01016-z |
| spellingShingle | Yuxuan Zhu Zhichao Huang Shichao Tian Qi Wang Fan Wu Jingwen Liu Ping Wang Hao Wan Liujing Zhuang Deming Jiang Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells Microsystems & Nanoengineering |
| title | Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells |
| title_full | Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells |
| title_fullStr | Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells |
| title_full_unstemmed | Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells |
| title_short | Nanocomposite biosensor tracks honokiol-induced oxidative stress dynamics in 3D hydrogel-cultured lung cancer cells |
| title_sort | nanocomposite biosensor tracks honokiol induced oxidative stress dynamics in 3d hydrogel cultured lung cancer cells |
| url | https://doi.org/10.1038/s41378-025-01016-z |
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