Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Nano Lett. 2013 Jun 12;13(6):2875-83. doi: 10.1021/nl401215n. Epub 2013 May 9.
A major goal in medical research is to develop artificial organelles that can implant in cells to treat pathological conditions or to support the design of artificial cells. Several attempts have been made to encapsulate or entrap enzymes, proteins, or mimics in polymer compartments, but only few of these nanoreactors were active in cells, and none was proven to mimic a specific natural organelle. Here, we show the necessary steps for the development of an artificial organelle mimicking a natural organelle, the peroxisome. The system, based on two enzymes that work in tandem in polymer vesicles, with a membrane rendered permeable by inserted channel proteins was optimized in terms of natural peroxisome properties and function. The uptake, absence of toxicity, and in situ activity in cells exposed to oxidative stress demonstrated that the artificial peroxisomes detoxify superoxide radicals and H2O2 after endosomal escape. Our artificial peroxisome combats oxidative stress in cells, a factor in various pathologies (e.g., arthritis, Parkinson's, cancer, AIDS), and offers a versatile strategy to develop other "cell implants" for cell dysfunction.
医学研究的一个主要目标是开发能够植入细胞的人工细胞器，以治疗病理状况或支持人工细胞的设计。已经有几种尝试将酶、蛋白质或模拟物包封或包裹在聚合物隔室中，但这些纳米反应器中只有少数在细胞中具有活性，并且没有一个被证明能模拟特定的天然细胞器。在这里，我们展示了开发模仿天然细胞器（过氧化物酶体）的人工细胞器的必要步骤。该系统基于在聚合物囊泡中串联工作的两种酶，并通过插入的通道蛋白使膜具有通透性，根据天然过氧化物酶体的特性和功能进行了优化。在暴露于氧化应激的细胞中摄取、无毒性和原位活性表明，人工过氧化物酶体能在胞内体逃逸后清除超氧自由基和 H2O2。我们的人工过氧化物酶体能抵抗细胞中的氧化应激，这是各种病理（如关节炎、帕金森病、癌症、艾滋病）的一个因素，并为开发其他用于细胞功能障碍的“细胞植入物”提供了一种通用策略。
