Intracellular reactive oxygen species (ROS) in steatotic cells pose a problem due to their potential to cause oxidative stress and cellular damage. Delivering engineered phospholipids to intracellular lipid droplets in steatotic hepatic cells, using the cell's inherent intracellular lipid transport mechanisms are investigated. Initially, it is shown that tail-labeled fluorescent lipids assembled into liposomes are able to be transported to intracellular lipid droplets in steatotic HepG2 cells and HHL-5 cells. Further, an antioxidant, an EUK salen–manganese derivative, which has superoxide dismutase-like and catalase-like activity, is covalently conjugated to the tail of a phospholipid and formulated as liposomes for administration. Steatotic HepG2 cells and HHL-5 cells incubated with these antioxidant liposomes have lower intracellular ROS levels compared to untreated controls and non-covalently formulated antioxidants. This first proof-of-concept study illustrates an alternative strategy to equip native organelles in mammalian cells with engineered enzyme activity.

中文翻译：

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用于清除脂肪肝细胞内活性氧的工程脂质


脂肪变性细胞中的细胞内活性氧（ROS）由于可能引起氧化应激和细胞损伤而造成问题。研究利用细胞固有的细胞内脂质转运机制将工程磷脂递送至脂肪肝细胞的细胞内脂滴。最初，研究表明组装成脂质体的尾部标记的荧光脂质能够转运到脂肪变性 HepG2 细胞和 HHL-5 细胞的细胞内脂滴。此外，一种抗氧化剂，一种 EUK salen-锰衍生物，具有超氧化物歧化酶样和过氧化氢酶样活性，与磷脂尾部共价结合，并配制成脂质体进行给药。与未经处理的对照和非共价配制的抗氧化剂相比，与这些抗氧化剂脂质体一起孵育的脂肪变性 HepG2 细胞和 HHL-5 细胞的细胞内 ROS 水平较低。这项第一项概念验证研究阐明了一种替代策略，为哺乳动物细胞中的天然细胞器配备工程酶活性。