| 초록 |
Multidrug resistance (MDR) is a leading cause of failure in current chemotherapy treatment and constitutes a formidable challenge in therapeutics. Here, we demonstrate that a nanoscale magnetic tandem apoptosis trigger (m-TAT), which consists of a magnetic nanoparticle and chemodrug (i.e., doxorubicin), can completely remove MDR cancer cells in both in vitro and in vivo systems. m-TAT simultaneously activates extrinsic and intrinsic apoptosis signals in a synergistic fashion and downregulates the drug efflux pump (i.e., P-glycoprotein) which is one of the main causes of MDR. The tandem apoptosis strategy uses only an extremely low level of chemodrug (in the nanomolar (nM) range) to completely eliminate MDR cancer cells. Our study indicates that nanoscale tandem activation of convergent signaling pathways is a new platform concept to overcome MDR with high efficacy and specificity. |
