Mucosa-penetrating NIR-II nanomedicine for precision photoimmunotherapy of bladder cancer.

Photoimmunotherapy has emerged as a promising modality in cancer treatment, but its effectiveness is limited by inadequate photoagent delivery and inflammation-induced immunosuppression. Herein, we developed an NIR-II-emitting mucosa-penetrating nanoplatform (LMPNCXB) for image-guided bladder cancer therapy. This nanoplatform integrates celecoxib (CXB), a cyclooxygenase-2 (COX-2) inhibitor, with an aggregation-induced emission luminogen (DCTBT) in a single optimized formulation. The positively charged surface formed by chitosan and cationic lipids enhances the nanoplatform's mucosal adhesion and penetration. Notably, owing to its pH- and ROS-responsive properties, it can selectively accumulate in tumors. The incorporated DCTBT serves both as an NIR-II imaging agent for precise tumor visualization and as an efficient photothermal converter, allowing targeted tumor ablation while simultaneously promoting the release of tumor-associated antigens. Simultaneously, the released CXB downregulates COX-2 expression, decreasing inflammation-induced immunosuppression to improve photoimmunotherapy. By reducing off-target drug accumulation in healthy tissues, this mucosal-administration nanoplatform presents an efficient, precise, and low-toxicity strategy for bladder cancer therapy.