Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation
The widespread use of engineered nanomaterials (ENMs) in food products necessitates the understanding of their impact on the gastrointestinal tract (GIT). Herein, we screened several representative food-borne comparator ENMs (i.e. ZnO, SiO2 and TiO2 nanoparticles (NPs)) and report that human colon c...
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/161848 |
| _version_ | 1824456925240098816 |
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| author | Wu, Zhuoran Setyawati, Magdiel Inggrid Lim, Hong Kit Ng, Kee Woei Tay, Chor Yong |
| author2 | School of Materials Science and Engineering |
| author_facet | School of Materials Science and Engineering Wu, Zhuoran Setyawati, Magdiel Inggrid Lim, Hong Kit Ng, Kee Woei Tay, Chor Yong |
| author_sort | Wu, Zhuoran |
| collection | NTU |
| description | The widespread use of engineered nanomaterials (ENMs) in food products necessitates the understanding of their impact on the gastrointestinal tract (GIT). Herein, we screened several representative food-borne comparator ENMs (i.e. ZnO, SiO2 and TiO2 nanoparticles (NPs)) and report that human colon cancer cells can insidiously exploit ZnO NP-induced adaptive response to acquire resistance against several chemotherapeutic drugs. By employing a conditioning and challenge treatment regime, we demonstrate that repeated exposure to a non-toxic dose of ZnO NPs (20 μM) could dampen the efficacy of cisplatin, paclitaxel and doxorubicin by 10-50% in monolayer culture and 3D spheroids of human colon adenocarcinoma cells. Structure-activity relationship studies revealed a complex interplay between nanoparticle surface chemistry and cell type in determining the chemoresistance-inducing effect, with silica coated ZnO NPs having a negligible influence on the anticancer treatment. Mechanistically, we showed that the pro-survival paracrine signaling was potentiated and propagated by a subset of ZnO NP "stressed" (Zn2++/ROS+) cells to the surrounding "bystander" (Zn2++/ROS-) cells. Transcriptome profiling, bioinformatics analysis and siRNA gene knockdown experiments revealed the nuclear factor erythroid 2-related factor 2 (Nrf2) as the key modulator of the ZnO NP-induced drug resistance. Our findings suggest that a ROS-inducing ENM can emerge as a nano-stressor, capable of regulating the chemosensitivity of colon cancer cells. |
| first_indexed | 2025-02-19T04:01:50Z |
| format | Journal Article |
| id | ntu-10356/161848 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T04:01:50Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1618482023-07-31T08:45:30Z Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation Wu, Zhuoran Setyawati, Magdiel Inggrid Lim, Hong Kit Ng, Kee Woei Tay, Chor Yong School of Materials Science and Engineering Nanyang Environment and Water Research Institute Environmental Chemistry and Materials Centre Engineering::Nanotechnology Nanomaterial Colon Cancer Cell The widespread use of engineered nanomaterials (ENMs) in food products necessitates the understanding of their impact on the gastrointestinal tract (GIT). Herein, we screened several representative food-borne comparator ENMs (i.e. ZnO, SiO2 and TiO2 nanoparticles (NPs)) and report that human colon cancer cells can insidiously exploit ZnO NP-induced adaptive response to acquire resistance against several chemotherapeutic drugs. By employing a conditioning and challenge treatment regime, we demonstrate that repeated exposure to a non-toxic dose of ZnO NPs (20 μM) could dampen the efficacy of cisplatin, paclitaxel and doxorubicin by 10-50% in monolayer culture and 3D spheroids of human colon adenocarcinoma cells. Structure-activity relationship studies revealed a complex interplay between nanoparticle surface chemistry and cell type in determining the chemoresistance-inducing effect, with silica coated ZnO NPs having a negligible influence on the anticancer treatment. Mechanistically, we showed that the pro-survival paracrine signaling was potentiated and propagated by a subset of ZnO NP "stressed" (Zn2++/ROS+) cells to the surrounding "bystander" (Zn2++/ROS-) cells. Transcriptome profiling, bioinformatics analysis and siRNA gene knockdown experiments revealed the nuclear factor erythroid 2-related factor 2 (Nrf2) as the key modulator of the ZnO NP-induced drug resistance. Our findings suggest that a ROS-inducing ENM can emerge as a nano-stressor, capable of regulating the chemosensitivity of colon cancer cells. Nanyang Technological University Published version Nanyang Technological University—Harvard School of Public Health Initiative for Sustainable Nanotechnology (NTU‐Harvard SusNano; NTU-HSPH-18002) 2022-09-21T08:20:30Z 2022-09-21T08:20:30Z 2022 Journal Article Wu, Z., Setyawati, M. I., Lim, H. K., Ng, K. W. & Tay, C. Y. (2022). Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation. Nanoscale. https://dx.doi.org/10.1039/d2nr03893e 2040-3364 https://hdl.handle.net/10356/161848 10.1039/d2nr03893e 36106385 en NTU-HSPH 18002 Nanoscale 10.21979/N9/GXLLW5 © 2022 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 unported Licence. application/pdf |
| spellingShingle | Engineering::Nanotechnology Nanomaterial Colon Cancer Cell Wu, Zhuoran Setyawati, Magdiel Inggrid Lim, Hong Kit Ng, Kee Woei Tay, Chor Yong Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title | Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title_full | Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title_fullStr | Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title_full_unstemmed | Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title_short | Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| title_sort | nanoparticle induced chemoresistance the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation |
| topic | Engineering::Nanotechnology Nanomaterial Colon Cancer Cell |
| url | https://hdl.handle.net/10356/161848 |
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