한빛사 논문
Abstract
Mi Hyeon Cho†‡§, Seulmi Kim†‡§, Jae-Hyun Lee†‡§, Tae-Hyun Shin†‡§, Dongwon Yoo†‡, and Jinwoo Cheon*†‡§
† Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
‡ Yonsei-IBS Institute, Yonsei University, Seoul 03722, Republic of Korea
§ Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
*Corresponding Author
Abstract
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.
Keywords: apoptosis; magnetic field; Magnetic nanoparticle; multidrug-resistant cancer; tandem activation
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