breast cancer, cell heterogeneity, microfluidic chips, single cell, ZnO NRs, Biotechnology, TP248.13-248.65, Materials of engineering and construction. Mechanics of materials, TA401-492

Abstract Zinc oxide nanorods have been extensively studied for the specific killing of breast cancer (BC) cells, and their killing mechanism and anticancer effects have been initially demonstrated. However, systematic studies at the single‐cell level are still necessary to explore cellular functions in detail. In this work, a hydrothermal method was used to synthesize zinc oxide nanorod arrays (ZnO NRs). Their effect on BC cells was demonstrated at single‐cell resolution for the first time through microfluidic chips and a single‐cell analysis platform. The inhibitory effects of ZnO NRs were observed. First, ZnO NRs suppressed cell proliferation and migration abilities. Moreover, Interferon‐γ, Tumor Necrosis Factor‐α, and Granzyme B in BC cells turned out to be antitumor instead of tumorigenic under ZnO NRs stimulation. Furthermore, ZnO NRs inhibition altered cellular functions and thus weakened intercellular and intercluster correlations. More importantly, MDA‐MB‐231 cells (strongly metastatic) showed much greater resistance to ZnO NRs than MCF‐7 cells (nonmetastatic). The experiments complemented the findings at the single‐cell level and provided a more comprehensive consideration of the potential risks and applications of ZnO NRs in breast cancer therapy, which is of great importance for biomedical research on nanomaterials.