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Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity.
Perche, F; Yi, Y; Hespel, L; Mi, P; Dirisala, A; Cabral, H; Miyata, K; Kataoka, K.
Affiliation
  • Perche F; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Yi Y; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Hespel L; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Mi P; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Dirisala A; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Cabral H; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Miyata K; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
  • Kataoka K; 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.
Biomaterials ; 90: 62-71, 2016 Jun.
Article in En | MEDLINE | ID: mdl-26986857
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyethylene Glycols / RNA, Small Interfering / Metal Nanoparticles / Gold / Hydroxychloroquine Limits: Humans Language: En Journal: Biomaterials Year: 2016 Document type: Article Affiliation country: Japan Country of publication: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyethylene Glycols / RNA, Small Interfering / Metal Nanoparticles / Gold / Hydroxychloroquine Limits: Humans Language: En Journal: Biomaterials Year: 2016 Document type: Article Affiliation country: Japan Country of publication: Netherlands