Bae Chun-Sik, Ahn Taeho
College of Veterinary Medicine, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
Lipids. 2018 Nov;53(11-12):1059-1067. doi: 10.1002/lipd.12124. Epub 2019 Jan 24.
Previous reports have suggested that cargo-free cationic nanoparticles (cNP) consisting of cationic monovalent lipids, such as 1,2-oleoyl-3-trimethylammonium-propane (DOTAP), induce reactive oxygen species (ROS) generation and toxicity in cells. In addition, cNP containing six lysine residues (6K) and cargo (6K-cNP) exerted synergistic effects on ROS production and cell death in cancer cells. In this study, we investigated the effect of diacylglycerol (DAG) derived from egg phosphatidylcholine in nanoparticles (NP) on ROS-mediated cellular toxicity. When DAG was incorporated into cNP (D-cNP) or 6K-cNP (6K-D-cNP) up to 7.8 mol% at the expense of DOTAP, and treated with cells, ROS generation in cancer cells increased further in a DAG concentration-dependent manner compared with those of both cNP without DAG. Concomitantly, cancer cell viability was more decreased upon the treatment with DAG-containing cNP. Moreover, D-cNP or 6K-D-cNP exhibited enhanced uptake into cells under endocytosis-inhibited conditions. Taken together, these results suggested that the presence of DAG in NP stimulated the interaction of NP with cancer cells and the resulting ROS-mediated cytotoxicity.
先前的报告表明，由阳离子单价脂质（如1,2-油酰基-3-三甲基铵丙烷（DOTAP））组成的无载药阳离子纳米颗粒（cNP）会诱导细胞内活性氧（ROS）的产生和毒性。此外，含有六个赖氨酸残基（6K）和载药的cNP（6K-cNP）对癌细胞中ROS的产生和细胞死亡具有协同作用。在本研究中，我们研究了纳米颗粒（NP）中源自鸡蛋磷脂酰胆碱的二酰基甘油（DAG）对ROS介导的细胞毒性的影响。当以DOTAP为代价将DAG掺入cNP（D-cNP）或6K-cNP（6K-D-cNP）中，使其含量高达7.8 mol%，并对细胞进行处理时，与不含DAG的两种cNP相比，癌细胞中ROS的产生以DAG浓度依赖性方式进一步增加。同时，用含DAG的cNP处理后，癌细胞活力下降得更多。此外，在抑制内吞作用的条件下，D-cNP或6K-D-cNP对细胞的摄取增强。综上所述，这些结果表明NP中DAG的存在促进了NP与癌细胞的相互作用以及由此产生的ROS介导的细胞毒性。
