Homologous Targeting and Adhesion Abilities of Cellular Microvesicles for Enhanced Intravesical Therapy of Bladder Cancer

Abstract

AbstractBladder cancer is one of the most common clinical malignant tumors with a high recurrence rate after surgery. To improve the therapeutic effect, intravesical instillation of chemotherapeutic drugs is usually applied after surgery. However, due to the unique microenvironment in the bladder, the drug concentration is usually rapidly reduced with urinary excretion, leading to low accumulation in bladder cancer and poor therapeutic effect. Cellular microvesicles (MVs) have parental cell‐specific characteristics and hold homologous targeting and adhesion abilities to their parent cells, achieving efficient cell uptake in their parent cells. In this study, pirarubicin (THP), a clinically approved intravesical chemotherapeutic drug, is encapsulated into bladder cancer cell‐derived MVs to form THPMVs, which have high targeting and adhesion abilities to bladder cancer and facilitate intravesical therapy of bladder cancer. The results show THPMVs compared with free THP exhibited higher cellular uptake in MB49 bladder cancer cells and cause more significant apoptotic cells. After intravesical instillation into a bladder cancer mouse model, THPMVs can significantly accumulate in bladder cancer tissues, and cause an obvious reduction in bladder weights and volumes, exhibiting promising therapeutic effects. Homologous targeting and adhesion abilities of THPMVs greatly contribute to the intravesical therapy of bladder cancer.