Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus, 8000, Denmark.
Small. 2016 Apr 6;12(13):1806-14. doi: 10.1002/smll.201502109. Epub 2016 Feb 8.
Cell mimicry is an approach which aims at substituting missing or lost activity. In this context, the goal of artificial organelles is to provide intracellularly active nanoreactors to affect the cellular performance. So far, only a handful of reports discuss concepts addressing this challenge based on single-component reactors. Here, the assembly of nanoreactors equipped with glucose oxidase (GOx)-loaded liposomal subunits coated with a poly(dopamine) polymer layer and RGD targeting units is reported. When comparing different surface modifications, the uptake of the nanoreactors by endothelial cells and macrophages with applied shear stress is confirmed without inherent cytotoxicity. Furthermore, the encapsulation and preserved activity of GOx within the nanoreactors is shown. The intracellular activity is demonstrated by exposing macrophages with internalized nanoreactors to glucose and assessment of the cell viability after 6 and 24 h. The macrophage viability is found to be reduced due to the intracellularly produced hydrogen peroxide by GOx. This report on the first intracellular active subcompartmentalized nanoreactors is a considerable step in therapeutic cell mimicry.
细胞模拟是一种旨在替代缺失或丧失功能的方法。在这种情况下，人工细胞器的目标是提供细胞内活性的纳米反应器来影响细胞性能。到目前为止，只有少数几篇报道讨论了基于单一组分反应器的解决这一挑战的概念。在这里，报告了一种纳米反应器的组装，该纳米反应器配备了载有葡萄糖氧化酶 (GOx) 的脂质体亚基，其表面涂有聚多巴胺 (poly(dopamine)) 聚合物层和 RGD 靶向单元。在比较不同的表面修饰时，证实了在施加切应力的情况下内皮细胞和巨噬细胞对纳米反应器的摄取，且没有固有细胞毒性。此外，还展示了纳米反应器内 GOx 的封装和保持活性。通过将内化了纳米反应器的巨噬细胞暴露于葡萄糖并在 6 和 24 小时后评估细胞活力，证明了细胞内的活性。由于 GOx 细胞内产生的过氧化氢，巨噬细胞的活力降低。本报告首次报道了细胞内活性亚区化纳米反应器，这是治疗性细胞模拟的重要一步。
