title: An epirubicin-conjugated nanocarrier with MRI function to overcome lethal multidrug-resistant bladder cancer.
abstract: Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ~1.8-fold (from 45 h to 81 h) at 37 °C, with a ~10-fold increase in concentration at the tumor site through magnetic targeting (MT). Moreover, malignant NDR bladder cancer can be effectively inhibited after 14 days in mice by just two injections and MT. We are the first to demonstrate the nanomedical strategy that can overcome the CMDR and NDR bladder cancers simultaneously, and proceed to the excellent MT therapy, significantly reducing the dosage and cardiotoxicity and holding great promise for incurable human MDR bladder cancer.
authors.affiliation: Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Mu-Yi
authors.initials: MY
authors.lastname: Hua
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Rung-Ywan
authors.initials: RY
authors.lastname: Tsai
authors.forename: See-Tong
authors.initials: ST
authors.lastname: Pang
authors.forename: Po-Hong
authors.initials: PH
authors.lastname: Hsu
authors.forename: Hsiang-Jun
authors.initials: HJ
authors.lastname: Tang
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Cheng-Keng
authors.initials: CK
authors.lastname: Chuang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003287:Contrast Media / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015251:Epirubicin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D019047:Phantoms, Imaging; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D003287:Contrast Media; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D015251:Epirubicin