1. Magnetic Tandem Apoptosis for Overcoming Multidrug-Resistant Cancer
- Author
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Jae Hyun Lee, Mi Hyeon Cho, Jinwoo Cheon, Dongwon Yoo, Tae Hyun Shin, and Seulmi Kim
- Subjects
Antineoplastic Agents ,Apoptosis ,Bioengineering ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,General Materials Science ,Doxorubicin ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Magnetite Nanoparticles ,Mice, Inbred BALB C ,010405 organic chemistry ,Chemistry ,Mechanical Engineering ,Intrinsic apoptosis ,Cancer ,General Chemistry ,Condensed Matter Physics ,medicine.disease ,Drug Resistance, Multiple ,0104 chemical sciences ,Multiple drug resistance ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,Female ,Efflux ,Signal transduction ,medicine.drug - 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.
- Published
- 2016