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Title: Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation
Authors: Wu, Zhuoran
Setyawati, Magdiel Inggrid
Lim, Hong Kit
Ng, Kee Woei
Tay, Chor Yong
Keywords: Engineering::Nanotechnology
Issue Date: 2022
Source: 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.
Project: NTU-HSPH 18002 
Journal: Nanoscale 
Abstract: 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.
ISSN: 2040-3364
DOI: 10.1039/d2nr03893e
DOI (Related Dataset): 10.21979/N9/GXLLW5
Schools: School of Materials Science and Engineering 
Research Centres: Nanyang Environment and Water Research Institute 
Environmental Chemistry and Materials Centre
Rights: © 2022 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 unported Licence.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:MSE Journal Articles
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