TY - JOUR
T1 - A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells
AU - Warashina, Shota
AU - Nakamura, Takashi
AU - Sato, Yusuke
AU - Fujiwara, Yuki
AU - Hyodo, Mamoru
AU - Hatakeyama, Hiroto
AU - Harashima, Hideyoshi
N1 - Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/3/10
Y1 - 2016/3/10
N2 - 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.
AB - 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.
KW - Cancer immunotherapy
KW - Dendritic cell
KW - Dendritic cell-based vaccine
KW - Endosomal escape
KW - SOCS1
KW - siRNA nanoparticle
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U2 - 10.1016/j.jconrel.2016.01.042
DO - 10.1016/j.jconrel.2016.01.042
M3 - Article
C2 - 26820519
AN - SCOPUS:84961330501
SN - 0168-3659
VL - 225
SP - 183
EP - 191
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -