title: An iron oxide nanocarrier for dsRNA to target lymph nodes and strongly activate cells of the immune system.
abstract: The success of nanoparticle-based therapies will depend in part on accurate delivery to target receptors and organs. There is, therefore, considerable potential in nanoparticles which achieve delivery of the right drug(s) using the right route of administration to the right location at the right time, monitoring the process by non-invasive molecular imaging. A challenge is harnessing immunotherapy via activation of Toll-like receptors (TLRs) for the development of vaccines against major infectious diseases and cancer. In immunotherapy, delivery of the vaccine components to lymph nodes (LNs) is essential for effective stimulation of the immune response. Although some promising advances have been made, delivering therapeutics to LNs remains challenging. It is here shown that iron-oxide nanoparticles can be engineered to combine in a single and small (<50 nm) nanocarrier complementary multimodal imaging features with the immunostimulatory activity of polyinosinic-polycytidylic acid (poly (I:C)). Whilst the fluorescence properties of the nanocarrier show effective delivery to endosomes and TLR3 in antigen presenting cells, MRI/SPECT imaging reveals effective delivery to LNs. Importantly, in vitro and in vivo studies show that, using this nanocarrier, the immunostimulatory activity of poly (I:C) is greatly enhanced. These nanocarriers have considerable potential for cancer diagnosis and the development of new targeted and programmable immunotherapies.
authors.affiliation: Theranostic Nanomedicine Laboratory, CIC biomaGUNE, Paseo Miramón 182, 20009, San Sebastián, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Cobaleda-Siles
authors.forename: Malou
authors.initials: M
authors.lastname: Henriksen-Lacey
authors.forename: Ane
authors.initials: A
authors.lastname: Ruiz de Angulo
authors.forename: Anja
authors.initials: A
authors.lastname: Bernecker
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gómez Vallejo
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Szczupak
authors.forename: Jordi
authors.initials: J
authors.lastname: Llop
authors.forename: Géraldine
authors.initials: G
authors.lastname: Pastor
authors.forename: Sandra
authors.initials: S
authors.lastname: Plaza-Garcia
authors.forename: Maite
authors.initials: M
authors.lastname: Jauregui-Osoro
authors.forename: Levente K
authors.initials: LK
authors.lastname: Meszaros
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mareque-Rivas
mesh_terms: D000818:Animals; D002460:Cell Line; D004337:Drug Carriers; D005290:Ferric Compounds / Q000008:administration & dosage*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D012330:RNA, Double-Stranded / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D012330:RNA, Double-Stranded; C000499:ferric oxide
keywords: Toll-like receptors; drug delivery; immunotherapy; multifunctional nanoparticles; multimodal imaging; theranostics