Research Organization for Nano & Life Innovation, Waseda University, Tokyo, Japan.
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Nanomedicine. 2018 Feb;14(2):279-288. doi: 10.1016/j.nano.2017.10.011. Epub 2017 Nov 8.
Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1β release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate the NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response.
含有赖氨酸头基和十四烷基、十六烷基或十八烷基谷氨酸疏水基团的阳离子脂质与/或丙基、戊基或庚基间隔物，被应用于使用简单的浴式超声仪制备阳离子脂质体。对脂质体的粒径分布、Zeta 电位、细胞内化和细胞毒性进行了表征，并通过检测白细胞介素-1β（IL-1β）的释放来评估其天然免疫刺激作用，如人巨噬细胞和 THP-1 细胞中的 NLRP3 炎性体激活。相比之下，由含有赖氨酸头基、十四烷基疏水链和丙基或戊基间隔物的脂质制成的 L3C14 和 L5C14 脂质体，最能激活 NLRP3 炎性体。可能的机制包括阳离子脂质体的内吞作用和随后的溶酶体破裂，而没有明显诱导活性氧的产生。总之，我们首次揭示了阳离子脂质体对 NLRP3 炎性体激活的结构影响，这为纳米颗粒在改善免疫反应中的应用提供了新的思路。
