title: Magnetic Tandem Apoptosis for Overcoming Multidrug-Resistant Cancer.
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.
authors.affiliation: 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.
authors.forename: Mi Hyeon
authors.initials: MH
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Seulmi
authors.initials: S
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Shin
authors.affiliation: Center for Nanomedicine, Institute for Basic Science (IBS) , Seoul 03722, Republic of Korea.|Yonsei-IBS Institute, Yonsei University , Seoul 03722, Republic of Korea.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Yoo
authors.affiliation: 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.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Cheon
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004317:Doxorubicin; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058185:Magnetite Nanoparticles; D008807:Mice, Inbred BALB C
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D004317:Doxorubicin
keywords: Magnetic nanoparticle; apoptosis; magnetic field; multidrug-resistant cancer; tandem activation