title: Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity.
abstract: Current technology of siRNA delivery relies on pharmaceutical dosage forms to route maximal doses of siRNA to the tumor. However, this rationale does not address intracellular bottlenecks governing silencing activity. Here, we tested the impact of hydroxychloroquine conjugation on the intracellular fate and silencing activity of siRNA conjugated PEGylated gold nanoparticles. Addition of hydroxychloroquine improved endosomal escape and increased siRNA guide strand distribution to the RNA induced silencing complex (RISC), both crucial obstacles to the potency of siRNA. This modification significantly improved gene downregulation in cellulo. Altogether, our data suggest the benefit of this modification for the design of improved siRNA delivery systems.
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Perche
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Hespel
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: P
authors.initials: P
authors.lastname: Mi
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Dirisala
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Cabral
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D006046:Gold / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006886:Hydroxychloroquine / Q000737:chemistry* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D006886:Hydroxychloroquine; D006046:Gold
keywords: Gold nanoparticles; Hydroxychloroquine; Intracellular bioavailability; siRNA delivery