1 research outputs found
Magnetic Tandem Apoptosis for Overcoming Multidrug-Resistant Cancer
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 (e.g.,
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 (e.g., P-glycoprotein) which is one of the main
causes of MDR. The tandem apoptosis strategy uses low level of chemodrug
(in the nanomolar (nM) range) to eliminate MDR cancer cells. We further
demonstrate that apoptosis of MDR cancer cells can be achieved in
a spatially selective manner with single-cell level precision. Our
study indicates that nanoscale tandem activation of convergent signaling
pathways is a new platform concept to overcome MDR with high efficacy
and specificity