Copper-based architectures for bladder cancer therapy: mechanistic insights, progress and prospects

Bladder cancer persists as a formidable clinical challenge due to its high recurrence rate, intrinsic chemoresistance, and suboptimal immunotherapy response. Copper-based nanomaterials have emerged as promising therapeutic platforms leveraging distinctive copper redox biology and tumor vulnerabilities to copper-induced cell death mechanisms-particularly cuproptosis. This review systematically analyzes dysregulated copper metabolism in bladder cancer and its mechanistic roles in mediating oxidative stress, ferroptosis, and cuproptosis, while classifying four principal nanomaterial categories: metallic Cu structures, copper-based polymers, copper-based compounds, and copper composites-highlighting their synthesis strategies, physicochemical properties, and therapeutic applications. These platforms facilitate photothermal, photodynamic and chemo-/immunotherapeutic synergies through precise modulation of redox homeostasis and tumor immunity. Despite these advances, key clinical translation barriers including biosafety concerns, pharmacokinetic variability, targeting inefficiency, immune unpredictability, and regulatory hurdles are critically examined. Future directions propose physics-informed material design, biomarker-guided patient stratification, and integrated therapy-monitoring platforms, demonstrating copper-based nanomedicine's significant potential to redefine precision intravesical therapy through mechanistically tailored, translationally optimized strategies.