title: MagRET Nanoparticles: An Iron Oxide Nanocomposite Platform for Gene Silencing from MicroRNAs to Long Noncoding RNAs.
abstract: Silencing of RNA to knock down genes is currently one of the top priorities in gene therapies for cancer. However, to become practical the obstacle of RNA delivery needs to be solved. In this study, we used innovative maghemite (γ-Fe2O3) nanoparticles, termed magnetic reagent for efficient transfection (MagRET), which are composed of a maghemite core that is surface-doped by lanthanide Ce(3/4+) cations using sonochemistry. Thereafter, a polycationic polyethylenimine (PEI) polymer phase is bound to the maghemite core via coordinative chemistry enabled by the [CeL(n)](3/4+)cations/complex. PEI oxidation was used to mitigate the in vivo toxicity. Using this approach, silencing of 80-100% was observed for mRNAs, microRNAs, and lncRNA in a variety of cancer cells. MagRET NPs are advantageous in hard to transfect leukemias. This versatile nanoscale carrier can silence all known types of RNAs and these MagRET NPs with oxidized PEI are not lethal upon injection, thus holding promise for therapeutic applications, as a theranostic tool.
authors.forename: E
authors.initials: E
authors.lastname: Lellouche
authors.forename: L L
authors.initials: LL
authors.lastname: Israel
authors.forename: M
authors.initials: M
authors.lastname: Bechor
authors.forename: S
authors.initials: S
authors.lastname: Attal
authors.forename: E
authors.initials: E
authors.lastname: Kurlander
authors.forename: V A
authors.initials: VA
authors.lastname: Asher
authors.forename: A
authors.initials: A
authors.lastname: Dolitzky
authors.affiliation: ∥Cancer Research Center, Sheba Medical Center, Ramat Gan 5262100, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Shaham
authors.affiliation: ∥Cancer Research Center, Sheba Medical Center, Ramat Gan 5262100, Israel.|⊥Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv 69978, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Izraeli
authors.forename: J-P
authors.initials: JP
authors.lastname: Lellouche
authors.forename: S
authors.initials: S
authors.lastname: Michaeli
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D004337:Drug Carriers; D005290:Ferric Compounds / Q000737:chemistry*; D020868:Gene Silencing; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D053761:Nanocomposites / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011094:Polyethyleneimine / Q000737:chemistry*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000499:ferric oxide; D011094:Polyethyleneimine