Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
College of Medicine, Nankai University, Tianjin 300071, China.
ACS Appl Mater Interfaces. 2021 May 12;13(18):21087-21096. doi: 10.1021/acsami.1c05512. Epub 2021 Apr 28.
The bottom-up construction of enzyme-based artificial cells is generating increasing interest, but achieving artificial cells for "all artificial modules" remains challenging in synthetic biology. Here, we introduce a fully synthetic cell system by integration of biomimetic nanozymes into giant unilamellar vesicles (GUVs). To mimic native peroxidase for free radical generation by taking advantage of Fenton catalysis reactions, we designed and prepared a de novo artificial nanozyme composed of ferritin heavy-chain scaffold protein and catalytic FeO nanoparticles as the active center. As two examples in bioapplications, we showed this nanozyme-powered GUV system not only mimics intracellular oxidative stress pathways but also induces tumor cell death by sensing and responding to external chemical signals. Specifically, we recreated intracellular biochemical events, including DNA damage and lipid peroxidation, in the compartmentalized GUVs by taking advantage of nanozyme induction of defined catalytic reactions. Additionally, the GUV system also actively induced DNA double-strand breakage and lipid damage of tumor cells, in response to the high expression of HO within the tumor microenvironment. This concept-of-proof study offers a promising option for defining catalysis in biological systems and gives new insights into the de novo creation of artificial cells in a fully synthetic manner.
基于酶的人工细胞的自下而上构建引起了越来越多的关注，但在合成生物学中实现“所有人工模块”的人工细胞仍然具有挑战性。在这里，我们通过将仿生纳米酶整合到巨大的单层囊泡（GUV）中，引入了一个完全合成的细胞系统。为了利用芬顿催化反应模拟天然过氧化物酶产生自由基，我们设计并制备了一种由铁蛋白重链支架蛋白和催化 FeO 纳米颗粒作为活性中心的新型人工纳米酶。作为生物应用的两个例子，我们表明，这种纳米酶驱动的 GUV 系统不仅模拟了细胞内氧化应激途径，而且通过感知和响应外部化学信号诱导肿瘤细胞死亡。具体来说，我们利用纳米酶诱导的特定催化反应，在分隔的 GUV 中重现了包括 DNA 损伤和脂质过氧化在内的细胞内生化事件。此外，GUV 系统还主动诱导肿瘤细胞的 DNA 双链断裂和脂质损伤，以响应肿瘤微环境中 HO 的高表达。这项概念验证研究为定义生物系统中的催化作用提供了一个有前途的选择，并为以完全合成的方式新创建人工细胞提供了新的见解。
