A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells

作者：Warashina Shota; Nakamura Takashi; Sato Yusuke; Fujiwara Yuki; Hyodo Mamoru; Hatakeyama Hiroto; Harashima Hideyoshi^*

来源：Journal of Controlled Release, 2016, 225: 183-191.

DOI：10.1016/j.jconrel.2016.01.042

• Cancer immunotherapy
• siRNA nanoparticle
• Dendritic cell
• Endosomal escape
• SOCS1
• Dendritic cell-based vaccine

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.

• 出版日期2016-3-10