In cancer immunotherapy, therapeutic methods targeting NK are highly expected. NK cell-based therapy using NK-92, a human NK cell line, has been clinically evaluated. Delivering mRNA into NK-92 cells is a potent strategy for enhancing its functions. However, the use of lipid nanoparticles (LNP) for this purpose has not yet been evaluated. We previously developed a LNP that was composed of CL1H6 (CL1H6-LNP) for the efficient delivery of siRNA to NK-92 cells, and the use of this material for delivering mRNA to NK-92 cells is reported in this study. Compared with a DLin-MC3-DMA based LNP, used as a benchmark, the CL1H6-LNP caused a high mRNA expression intensity and a cell transfection efficiency of 100%. The efficient mRNA delivery by this CL1H6-LNP is attributed to the high affinity for NK-92 cells and the intense, rapid fusion with the endosomal membrane. It therefore appears that the CL1H6-LNP could be a useful non-viral vector for modifying the NK-92 functions by mRNA. Our findings also provide some insights into the design and development of LNPs for delivering mRNA to NK-92 and NK cells.

在癌症免疫治疗中，靶向 NK 的治疗方法备受期待。使用人类 NK 细胞系 NK-92 的基于 NK 细胞的疗法已经过临床评估。将 mRNA 递送到 NK-92 细胞是增强其功能的有效策略。然而，尚未评估为此目的使用脂质纳米颗粒 (LNP)。我们之前开发了一种由 CL1H6 (CL1H6-LNP) 组成的 LNP，用于将 siRNA 有效递送至 NK-92 细胞，本研究报告了使用这种材料将 mRNA 递送至 NK-92 细胞。与用作基准的基于 DLin-MC3-DMA 的 LNP 相比，CL1H6-LNP 导致了高 mRNA 表达强度和 100% 的细胞转染效率。这种 CL1H6-LNP 的有效 mRNA 递送归因于对 NK-92 细胞的高亲和力和强烈的，与内体膜快速融合。因此，看来 CL1H6-LNP 可能是一种有用的非病毒载体，可用于通过 mRNA 修饰 NK-92 功能。我们的研究结果还为用于将 mRNA 递送至 NK-92 和 NK 细胞的 LNP 的设计和开发提供了一些见解。