Nanoparticle-induced chemoresistance: the emerging modulatory effects of engineered nanomaterials on human intestinal cancer cell redox metabolic adaptation. Issue 39 (15th September 2022)

• Record Type: Journal Article
• Authors: Wu, Zhuoran; Setyawati, Magdiel Inggrid; Lim, Hong Kit; Ng, Kee Woei; Tay, Chor Yong
• Is Part Of: Nanoscale. Volume 14:Issue 39(2022)
• Page Start: 14491
• Page End: 14507
• Publication Date: 2022-09-15
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d2nr03893e
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Exposure to non-cytotoxic doses of engineered nanomaterials induce reactive oxygen species stress response cascades in human intestinal cancer cells to resist chemotherapeutics. 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" (Zn 2+ +/ROS+) cells to the surrounding "bystander" (Zn 2+ +/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.