Nanomaterial-Enhanced Immunotherapy: Advancing T-Cell-Based Treatments for Bladder Cancer

Bladder cancer (BC) is a prevalent urinary malignancy characterized by high recurrence rates and suboptimal long-term outcomes from traditional treatments such as surgery, chemotherapy, and radiotherapy. T-cell-based immunotherapy has emerged as a promising approach, harnessing T cells' capacity to target and destroy tumor cells, yet it faces challenges from the immunosuppressive tumor microenvironment (TME), immune evasion, and T-cell exhaustion. Nanomaterials offer innovative solutions by enabling targeted delivery of antigens, checkpoint inhibitors, and immunomodulators; remodeling the TME through metabolic interventions (eg, hypoxia alleviation and adenosine reduction); and enhancing T-cell infiltration and persistence with stimulus-responsive systems like pH-sensitive nanoparticles and biomimetic vesicles. This review systematically examines nanomaterial integration to amplify T-cell-mediated immunity in BC, covering T-cell origins, differentiation (eg, CD8+ cytotoxic and CD4+ helper subsets), roles in the TME, and exhaustion mechanisms driven by factors like PD-1 and TOX. We discuss key strategies including direct immune enhancement via immunogenic cell death induction, metabolic reprogramming to optimize T-cell function, and sustained activation for improved persistence. In conclusion, these nanomaterial-enhanced therapies address critical barriers, promoting precise and synergistic immune responses. Future prospects highlight AI-driven designs, personalized medicine, and clinical translation to tackle heterogeneity, biosafety, and resistance for durable BC remission.