2024-03-28T20:53:45Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/646902022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124A lipid nanoparticle for the efficient delivery of siRNA to dendritic cellsWarashina, ShotaNakamura, TakashiSato, YusukeFujiwara, YukiHyodo, MamoruHatakeyama, HirotoHarashima, HideyoshiCancer immunotherapysiRNA nanoparticleDendritic cellEndosomal escapeSOCS1Dendritic cell-based vaccine499Applying 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.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/64690https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/64690/1/JCR%20225.%20183-191%2c%202016%20HUSCAP.pdf0168-3659Journal of controlled release2251831912016-03-10enginfo:pmid/26820519info:doi/10.1016/j.jconrel.2016.01.042©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/author