Dual delivery nanoscale device for miR-451 and adriamycin co-delivery to combat multidrug resistant in bladder cancer.

The outcome of current cancer therapy is usually impeded by complicated extracellular and intracellular barriers. Most importantly, untargeted distribution and multidrug resistance (MDR) are considered as two important difficulties responsible for the poor performance of many currently available drug delivery systems (DDS). As a result, in our study, we developed a cancer cell membrane (CM) coated calcium carbonate (CC) nanoparticles to co-delivery miR-451 with adriamycin (Adr) to address the dilemma occurred in the therapy of bladder cancer (MCC/R-A). The homologous CCM from MDR bladder cancer cells (BIU-87/Adr) was employed to increase targeted retention of DDS within the tumor tissue and to bypass the extracellular barriers. Moreover, the MDR of cancer cells was conquered through downregulation of P-gp expression using miR-451 since it was confirmed by previous reports that miR-451 could significantly downregulate the level of P-gp in MDR cells, which in turn elevated the cellular drug retention in BIU-87/Adr. Our in vitro and in vivo experiments have revealed that MCC/R-A showed a greatly enhanced therapeutic effect on BIU-87/Adr, which was superior than applying miR-451 or Adr alone. The preferable effect of MCC/R-A on conquering the MDR in bladder cancer provides a novel alternative for effective chemotherapy of MDR cancers.