Liposome-Encapsulated Bacillus Calmette–Guérin Cell Wall Skeleton Enhances Antitumor Efficiency for Bladder Cancer In Vitro and In Vivo via Induction of AMP-Activated Protein Kinase

摘要

We engineered novel nanoparticles consisting of liposome-encapsulated Bacillus Calmette–Guérin cell well skeleton (BCG-CWS) for intravesical instillation in bladder cancer. The liposome-encapsulated BCG-CWS nanoparticles had antitumoral effects in an orthotopic bladder cancer mouse model, and the BCG-CWS nanoparticles can be further developed as a non-toxic substitute for live BCG with improved dispensability, stability, and size compatibility. This is significant because we succeeded in the intravesical delivery of BCG-CWS through the intravesical route using a catheter in an orthotopic bladder cancer mouse model to specifically target tumor cells. This is the first study on the BCG-CWS-induced activation of AMPK in urothelial carcinoma cells, suggesting that AMPK-mediated reactive oxygen species (ROS) production and ER stress is a cellular signaling pathway in tumors sensitive to BCG-CWS. These results have the potential for significant ramifications in targeted therapy using a predictive marker for bladder cancer.