title: In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model.
abstract: miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe₃O₄ nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADR(fluc) tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China. wind8828@gmail.com.
authors.forename: Zhongchan
authors.initials: Z
authors.lastname: Sun
authors.forename: Xinxing
authors.initials: X
authors.lastname: Song
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Shun
authors.initials: S
authors.lastname: Qi
authors.forename: Ruirui
authors.initials: R
authors.lastname: Qiao
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Huan
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000494:pharmacology; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000737:chemistry / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; C505362:MIRN16 microRNA, human; D058185:Magnetite Nanoparticles; D035683:MicroRNAs; D004317:Doxorubicin; D007501:Iron; D052203:Ferrosoferric Oxide