Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Int J Pharm. 2023 Apr 5;636:122810. doi: 10.1016/j.ijpharm.2023.122810. Epub 2023 Mar 8.
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.
在癌症免疫疗法中，针对自然杀伤 (NK) 细胞的治疗方法备受期待。利用人 NK 细胞系 NK-92 的 NK 细胞疗法已在临床上进行了评估。向 NK-92 细胞中递送 mRNA 是增强其功能的有效策略。然而，尚未对此目的使用脂质纳米颗粒 (LNP) 进行评估。我们之前开发了一种由 CL1H6（CL1H6-LNP）组成的 LNP，用于将 siRNA 高效递送至 NK-92 细胞，本研究报告了使用该材料将 mRNA 递送至 NK-92 细胞的情况。与用作基准的基于 DLin-MC3-DMA 的 LNP 相比，CL1H6-LNP 引起的 mRNA 表达强度和细胞转染效率均为 100%。CL1H6-LNP 高效递送 mRNA 归因于其对 NK-92 细胞的高亲和力以及与内体膜的强烈、快速融合。因此，CL1H6-LNP 似乎可以成为一种有用的非病毒载体，通过 mRNA 修饰 NK-92 的功能。我们的研究结果还为设计和开发用于向 NK-92 和 NK 细胞递送 mRNA 的 LNP 提供了一些见解。
