Bioadhesive ZnO2@BCG synergizing chemodynamic-immunotherapy enhances bladder cancer treatment

For patients with high-risk non-muscle-invasive bladder cancer (NMIBC), intravesical Bacillus Calmette-Guérin (BCG) is a well-established first-line therapy. However, disease recurrence and progression remain major clinical challenges. In this study, leveraging the inherently negative charge of biofilms, we constructed a ZnO 2 @BCG conjugate via charge-driven self-assembly of polyethyleneimine-modified ZnO 2 and BCG. ZnO 2 @BCG enhances its adhesion to the bladder wall through its own positive charge, thereby promoting sustained tumor killing. Mechanistically, ZnO 2 @BCG activates the pyroptosis pathway through the canonical inflammasome signaling cascade. The synergistic interplay between ZnO 2 -induced immunogenic cell death (ICD) and BCG immunotherapy promotes dendritic cell (DC) maturation and M1 macrophage polarization, effectively inhibiting tumor progression and extending a prolonged survival in an orthotopic murine bladder cancer model. Furthermore, the formulation exhibits an enhanced tolerability and biosafety. Thus, our work proposes a novel therapeutic strategy for bladder cancer by integrating ZnO 2 -based chemodynamic therapy with BCG immuno-instillation.