Current cancer therapy usually succumbs to many extracellular and intracellular barriers, among which untargeted distribution and multidrug resistance (MDR) are two important difficulties responsible for poor outcome of many drug delivery systems (DDS). Here, in our study, the dilemma was addressed by developing a cancer cell membrane (CCM)-coated silica (SLI) nanoparticles to co-deliver miR495 with doxorubicin (DOX) for effective therapy of lung cancer (CCM/SLI/R-D). The homologous CCM from MDR lung cancer cells (A549/DOX) was supposed to increase the tumor-homing property of the DDS to bypass the extracellular barriers. Moreover, the MDR of cancer cells were conquered through downregulation of P-glycoprotein (P-gp) expression using miR495. It was proved that miR495 could significantly decrease the expression of P-gp which elevated intracellular drug accumulation in A549/DOX. The in vitro and in vivo results exhibited that CCM/SLI/R-D showed a greatly enhanced therapeutic effect on A549/DOX, which was superior than applying miR495 or DOX alone. The preferable effect of CCM/SLI/R-D on conquering the MDR in lung cancer provides a novel alternative for effective chemotherapy of MDR cancers.
Keywords: Cancer cell membrane; Doxorubicin; Drug resistance; Lung cancer therapy; Silica nanoparticle; miR495.