Magnetic Tandem Apoptosis for Overcoming Multidrug-Resistant Cancer

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• 作者：Mi Hyeon Cho ; Seulmi Kim ; Jae-Hyun Lee ; Tae-Hyun Shin ; Dongwon Yoo ; Jinwoo Cheon
• 刊名：Nano Letters
• 出版年：2016
• 出版时间：December 14, 2016
• 年：2016
• 卷：16
• 期：12
• 页码：7455-7460
• 全文大小：495K
• ISSN：1530-6992

文摘

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.