Department of Micro- and Nanotechnology, Center for Nanomedicine and Theranostics, DTU Nanotech, Technical University of Denmark, Building 423, 2800, Lyngby, Denmark.
Adv Healthc Mater. 2017 Feb;6(4). doi: 10.1002/adhm.201601190. Epub 2016 Dec 22.
The creation of artificial organelles is a new paradigm in medical therapy that aims to substitute for missing cellular function by replenishing a specific cellular task. Artificial organelles tackle the challenge of mimicking metabolism, which is the set of chemical reactions that occur within a cell, mainly catalyzed by enzymes. So far, the few reported carriers able to conduct enzymatic reactions intracellularly are based on single-compartment carriers. However, cell organelles outperform by conducting multiple reactions simultaneously within confined sub-compartments. Here, the field of artificial organelles is advanced by reporting the assembly of a microreactor consisting of polymer capsules entrapping gold nanoclusters (AuNCs) and liposomes as sub-compartments. The fluorescence properties of AuNCs are employed to monitor the microreactors uptake by macrophages. Encapsulation is demonstrated and functionality of microreactors with trypsin (TRP) and horseradish peroxidase (HRP)-loaded liposomes is preserved. Multiple enzymatic reactions taking place simultaneously is demonstrated by exposing macrophages with the internalized microreactors to bis-(benzyloxycarbonyl-Ile-Pro-Arg)-Rho-110 and Amplex Red substrates, which are specific for TRP and HRP, respectively. Conversion of the substrates into the respective fluorescent products is observed. This report on the first microreactor conducting multiple enzymatic reactions simultaneously inside a cell is a considerable step in the field of artificial organelles.
人工细胞器的构建是医学治疗中的一个新范例，旨在通过补充特定的细胞任务来替代缺失的细胞功能。人工细胞器解决了模拟代谢的挑战，代谢是细胞内发生的一系列化学反应，主要由酶催化。到目前为止，能够在细胞内进行酶反应的少数报道的载体基于单室载体。然而，细胞器通过在受限的亚室中同时进行多个反应而表现出色。在这里，通过报告由聚合物胶囊包封金纳米簇（AuNCs）和脂质体作为亚室的微反应器的组装，推进了人工细胞器领域。AuNCs 的荧光性质用于监测巨噬细胞对微反应器的摄取。封装得到了证明，并且负载有胰蛋白酶（TRP）和辣根过氧化物酶（HRP）的脂质体的微反应器的功能得以保留。通过将内化的微反应器暴露于双（苄氧羰基-Ile-Pro-Arg）-Rho-110 和 Amplex Red 底物（分别针对 TRP 和 HRP），来证明同时发生的多个酶反应。观察到将底物转化为各自的荧光产物。本报告是第一个在细胞内同时进行多个酶反应的微反应器，是人工细胞器领域的重要进展。
