A hypoxic microfluidic organoid-on-a-chip system for studying the efficacy of metronidazole-modified nanomaterials against cholangiocarcinoma established within the chip

<2.5%), evidenced by the robust upregulation of HIF-1α and HIF-2α. Furthermore, BMMNP NPs demonstrated superior cellular uptake and potent cytotoxicity within the hypoxic CCOs. Notably, these nanoparticles effectively reversed hypoxia-induced resistance to gemcitabine, acting as a powerful chemosensitizer. Collectively, this platform not only establishes a physiologically relevant "hypoxia-on-a-chip" model for preclinical drug evaluation but also accelerates the optimization of nanoparticle-based strategies for hypoxia-targeted therapy.