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Title
  • en A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells
Creator
Accessrights open access
Rights
  • en ©2016 , Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
  • http://creativecommons.org/licenses/by-nc-nd/4.0/
  • en Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Subject
  • Other en Cancer immunotherapy
  • Other en siRNA nanoparticle
  • Other en Dendritic cell
  • Other en Endosomal escape
  • Other en SOCS1
  • Other en Dendritic cell-based vaccine
  • NDC 499
Description
  • Abstract en Applying small interfering RNA (siRNA) to dendritic cell (DC) based therapy represents a potential candidate for cancer immunotherapy. However, delivering siRNA to DCs is a challenging issue for non-viral vectors. To date, only viral vectors have achieved efficient gene silencing in DCs. We report herein that a novel cationic lipid, YSK12-C4, when loaded in a nanoparticle with siRNA (YSK12-C4 multifunctional envelope type nano device [YSK12-MEND]), greatly facilitated gene silencing in mouse DCs. The use of the YSK12-MEND resulted in a gene silencing efficiency in excess of 90%, with a median effective dose (ED50) of 1.5 nM, whereas the maximum gene silencing efficiency of Lipofectamine RNAiMAX was less than 60% and the ED50 was 25 nM. Furthermore, suppressor of cytokine signaling 1, an immune suppressive molecule in DCs, silenced in the mouse DC by the YSK12-MEND showed a drastic enhancement in cytokine production, resulting in the significant suppression of tumor growth when it was applied to DC-based therapy against a mouse lymphoma. These results clearly indicate that YSK12-MEND overcomes the obstacle associated with non-viral vectors and can be considered to be a promising non-viral vector for siRNA delivery to DCs, thus accelerating DC-based therapies with siRNA. (C) 2016 Elsevier B.V. All rights reserved.
Publisher en Elsevier
Date
    Issued2016-03-10
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/64690
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.jconrel.2016.01.042
  • PMID 26820519
Journal
    • PISSN 0168-3659
      • en Journal of controlled release
      • Volume Number225 Page Start183 Page End191
File
Oaidate 2023-07-26