title: Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells.
abstract: We demonstrate a straightforward method to encapsulate siRNA into naturally available and unmodified human apoferritin. The encapsulation into apoferritin is independent of the sequence of the siRNA and provides superior protection for those sensitive molecules. High efficiency in transfection can be achieved in human tumorigenic cells, human primary mesenchymal stem cells (hMSC) and peripheral blood mononuclear cells (PBMCs). In contrast to Lipofectamine, highly effective gene silencing can be achieved with ferritin as the delivery agent in both tumor cells and PBMCs at low siRNA concentrations (10 nM). As an endogenous delivery agent, apoferritin does not induce immune activation of T- and B-cells in human PBMCs. Apoferritin shows intrinsic anti-inflammatory effects and apoferritin-mediated delivery shows a preference for immune-activated T- and B-cells, a natural selectivity which may turn useful for drug delivery in case of infections or inflammatory diseases.
authors.affiliation: CIC nanoGUNE, Tolosa Hiribidea 76, 20018 Donostia-San Sebastian, Spain.
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.affiliation: Biodonostia Health Research Institute, Paseo Dr. Begiristain s/n, 20014 Donostia-San Sebastian, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Muñoz-Culla
authors.affiliation: CIC nanoGUNE, Tolosa Hiribidea 76, 20018 Donostia-San Sebastian, Spain.
authors.forename: Unai
authors.initials: U
authors.lastname: Carmona
authors.affiliation: Fundación Inbiomed, Paseo Mikeletegi 81, 20009 Donostia-San Sebastian, Spain.
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Lopez
authors.affiliation: CIC nanoGUNE, Tolosa Hiribidea 76, 20018 Donostia-San Sebastian, Spain.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Fundación Inbiomed, Paseo Mikeletegi 81, 20009 Donostia-San Sebastian, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Trigueros
authors.affiliation: Biodonostia Health Research Institute, Paseo Dr. Begiristain s/n, 20014 Donostia-San Sebastian, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Otaegui
authors.affiliation: School of Life Sciences, Northwestern Polytechnical University, 710072 Xi'an, China; CIC nanoGUNE, Tolosa Hiribidea 76, 20018 Donostia-San Sebastian, Spain. Electronic address: l.zhang@nanogune.eu.
authors.forename: Lianbing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: CIC nanoGUNE, Tolosa Hiribidea 76, 20018 Donostia-San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Spain. Electronic address: m.knez@nanogune.eu.
authors.forename: Mato
authors.initials: M
authors.lastname: Knez
mesh_terms: D018938:Caco-2 Cells; D005293:Ferritins / Q000378:metabolism*; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D005293:Ferritins
keywords: Drug delivery; Ferritin; Gene silencing; Primary cells; siRNA