Title |
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A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells
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Creator |
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Accessrights |
open access |
Rights |
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©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/
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
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Subject |
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Other
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Cancer immunotherapy
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Other
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siRNA nanoparticle
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Other
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Dendritic cell
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Other
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Endosomal escape
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Other
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SOCS1
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Other
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Dendritic cell-based vaccine
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NDC
499
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Description |
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Abstract
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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.
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Publisher |
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Elsevier
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Date |
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Language |
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Resource Type |
journal article |
Version Type |
AM |
Identifier |
HDL
http://hdl.handle.net/2115/64690
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Relation |
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isVersionOf
DOI
https://doi.org/10.1016/j.jconrel.2016.01.042
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PMID
26820519
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Journal |
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Journal of controlled release
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Volume Number225
Page Start183
Page End191
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File |
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Oaidate |
2023-07-26 |