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A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells
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| Title: | A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells |
| Authors: | Warashina, Shota Browse this author | | Nakamura, Takashi Browse this author →KAKEN DB | | Sato, Yusuke Browse this author →KAKEN DB | | Fujiwara, Yuki Browse this author | | Hyodo, Mamoru Browse this author →KAKEN DB | | Hatakeyama, Hiroto Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | Cancer immunotherapy | | siRNA nanoparticle | | Dendritic cell | | Endosomal escape | | SOCS1 | | Dendritic cell-based vaccine |
| Issue Date: | 10-Mar-2016 |
| Publisher: | Elsevier |
| Journal Title: | Journal of controlled release |
| Volume: | 225 |
| Start Page: | 183 |
| End Page: | 191 |
| Publisher DOI: | 10.1016/j.jconrel.2016.01.042 |
| PMID: | 26820519 |
| Abstract: | 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. |
| Rights: | ©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/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/64690 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 中村 孝司
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