Abstract
In bladder cancer, metabolic dysregulation of reactive oxygen species (ROS) promotes malignant transformation through oxidative DNA damage while concurrently activating pro-survival pathways such as NF-κB. To address this, we developed a synergistic therapeutic platform by incorporating gold nanoparticles into cerium oxide nanostructures (Au/CeO₂) with enhanced antioxidant activity, followed by loading with astragaloside IV (Au/CeO₂@As). The core-shell structured Au/CeO₂@As nanocomposites demonstrated remarkable pro-apoptotic effects, exhibiting a 5.11-fold increase in apoptosis induction compared to free astragaloside IV alone. Subsequent cell proliferation assays confirmed the system's ability to effectively inhibit tumor cell migration and proliferation. Mechanistic investigations through qPCR and Western blot analyses revealed that Au/CeO₂@As mediates its antitumor effects through coordinated regulation of the STAT3 and NF-κB signaling pathways, leading to significant tumor cell damage. Importantly, the Au/CeO₂@As nanocomposites did not exhibit significant cytotoxicity while demonstrating excellent therapeutic efficacy. These findings collectively establish Au/CeO₂@As as a highly promising nanotherapeutic candidate for bladder cancer treatment, offering both targeted ROS modulation and specific pathway regulation capabilities.