Zn-Quer Nanozymes Reprogram the Malignant Phenotypic Transformation of Gastric Cancer Cells via Cascade Reactive Oxygen Species Coordination

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, presenting significant therapeutic challenges due to its late-stage diagnosis and high metastatic potential. Imbalance in reactive oxygen species (ROS) homeostasis is crucial for the onset, development, and malignant transformation of GC. To address the demand for innovative therapeutic approaches, this study introduces a novel nanocoordination polymer, Zn-Quer nanozymes (NZs), synthesized from quercetin (Quer) and zinc ions. These nanoparticles utilize quercetin's anti-inflammatory and antioxidant properties, improving its bioavailability and therapeutic effectiveness via a nanoparticle delivery system. Zn-Quer NZs were synthesized via coordination chemistry and characterized by using TEM, XRD, and FTIR to confirm their structural integrity and composition. In vitro studies on GC cell lines and in vivo xenograft model experiments demonstrate that Zn-Quer NZs effectively inhibit cell proliferation, induce apoptosis, and reprogram malignant phenotypes such as epithelial-mesenchymal transition (EMT) and angiogenesis, as indicated by changes in the expression of related markers. Moreover, Zn-Quer NZs significantly reduce the overall intracellular ROS levels in epithelial cells under oxidative stress by modulating multiple steps of ROS generation. These findings underscore Zn-Quer NZs as a promising therapeutic strategy for gastric cancer, capable of rebalancing ROS and effectively reversing malignant phenotypic transformation.