To address the clinical challenges of limited therapeutic efficacy and pronounced toxicity associated with conventional intravesical chemotherapy due to the bladder mucosal barrier, this study constructs an extracellular vesicles (EVs)-based drug delivery system loaded with pirarubicin (THP), designated as EVs@THP. EVs derived from MB49 bladder tumor cells were extracted by ultracentrifugation and loaded with THP. Structural characterization confirmed that EVs@THP maintained stable vesicle structure. In vitro cell experiments showed that EVs@THP could be efficiently internalized by bladder cancer cells and presented stronger tumor killing ability compared with free THP. In vivo experiments using orthotopic bladder cancer mouse models further proved that EVs@THP possessed better tissue penetration and intravesical retention after perfusion, with significantly superior antitumor efficacy to free THP. MB49 cell-derived EVs are promising delivery carriers for THP. The EVs@THP system with good biocompatibility and targeting ability can effectively improve the outcome of bladder cancer intravesical chemotherapy, providing experimental evidence for the development and transformation of novel intravesical therapeutic regimens.
