Cellular AND Gates: Synergistic Recognition to Boost Selective Uptake of Polymeric Nanoassemblies
Cellular AND Gates: Synergistic Recognition to Boost Selective Uptake of Polymeric Nanoassemblies
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DOI：
10.1002/anie.202002748
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发表时间：
2020-04-15
影响因子：
16.6
通讯作者：
Thayumanavan, S.
中科院分区：
文献类型：
--
作者：
Gao, Jingjing;Wu, Peidong;Thayumanavan, S.
基于纳米粒子的生物医学应用的发展由于不期望的脱靶效应而受到阻碍。在此，我们概述了一个细胞AND门，以提高摄取选择性，其中纳米组装-细胞相互作用被打开，只有在两种不同的蛋白质功能同时存在时，酶反应（碱性磷酸酶，ALP）和配体-蛋白质（碳酸酐酶IX， CA IX）结合事件。在过表达这两种蛋白质（单细胞和门）的细胞中观察到选择性摄取纳米组件。有趣的是，在CA IX过表达的细胞中，当与ALP过表达的细胞共培养时，也可以实现选择性摄取，其中纳米组装可能作为细胞-细胞通信的介质（双细胞AND门）。这种逻辑门控细胞摄取可以在诸如肿瘤成像或治疗学等应用中找到用途。
The development of nanoparticle-based biomedical applications has been hampered due to undesired off-target effects. Herein, we outline a cellular AND gate to enhance uptake selectivity, in which a nanoassembly-cell interaction is turned on, only in the concurrent presence of two different protein functions, an enzymatic reaction (alkaline phosphatase, ALP) and a ligand-protein (carbonic anhydrase IX, CA IX) binding event. Selective uptake of nanoassemblies was observed in cells that overexpress both of these proteins (unicellular AND gate). Interestingly, selective uptake can also be achieved in CA IX overexpressed cells, when cocultured with ALP overexpressed cells, where the nanoassembly presumably acts as a mediator for cell-cell communication (bicellular AND gate). This logic-gated cellular uptake could find use in applications such as tumor imaging or theranostics.