期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 609, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121140
关键词
Non-viral; Lipid nanoparticle; siRNA; pH-sensitive cationic lipid; NK cell; NK-92
资金
- JSPS KAKENHI [20H03373]
- Special Education and Research Expenses from the Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [20H03373] Funding Source: KAKEN
The development of CL1H6-LNP offers a promising approach for efficient gene silencing in NK-92 cells with low cytotoxicity. The results suggest that CL1H6-LNP has the potential for delivering siRNA to NK-92 cells.
The use of natural killer (NK) cells in cell therapy is an attractive next generation strategy for cancer immunotherapy. NK-92 cells (a human NK cell line) have been tested in clinical trial stages, making them an off-theshelf medicine. Controlling gene expression in NK-92 cells by an artificial delivery system is an available for enhancing NK-92 cell therapy. We report here on the development of a siRNA-loaded lipid nanoparticle (LNP) composed of CL1H6 (CL1H6-LNP), an optimized, pH-sensitive cationic lipid, with efficient gene silencing and low cytotoxicity in NK-92 cells. The hydrophilic head group of the lipid molecule used in preparing these particles largely influences the pKa of the final LNP, and lipids with an amino moiety substituted with a methyl group showed a high gene silencing activity. Compared with myristate and palmitate, the hydrophobic tail of oleate had a high gene silencing activity and cell viability. Analyses of intracellular trafficking indicated that the CL1H6-LNP appeared to escape from the endosomes via membrane fusion, without disrupting the membrane. The mechanism of endosomal escape should contribute to our understanding of efficient gene silencing with a low degree of cytotoxicity. These results therefore suggest that a CL1H6-LNP has promise for delivering siRNA to NK-92 cells.
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