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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
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
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 中村 孝司

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