Logic-Gated Cell-Derived Nanovesicles via DNA-Based Smart Recognition Module
Logic-Gated Cell-Derived Nanovesicles via DNA-Based Smart Recognition Module
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DOI：
10.1021/acsami.1c07632
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发表时间：
2021-06-23
影响因子：
9.5
通讯作者：
Tan, Weihong
中科院分区：
文献类型：
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作者：
Huang, Huidong;Guo, Zhenzhen;Tan, Weihong
构建具有主动靶向配体的细胞源性纳米囊泡是提高靶向效率的重要策略。然而，与靶细胞的结合能力增强也导致与共享相同生物标志物的非靶细胞的结合。基于DNA的逻辑门是一种分子系统，通过产生输出信号来响应化学输入，并且输入和输出之间的关系基于一定的逻辑。因此，基于DNA的逻辑门可以提供一种新的方法来提高纳米囊泡的递送效率。在这项工作中，我们开发了一种DNA逻辑门控模块，其偶联两种肿瘤细胞靶向因子（例如，低pH和肿瘤细胞生物标志物）。将该模块固定在纳米囊泡的表面上使得纳米囊泡能够感测肿瘤细胞靶向因子并将这些线索视为输入AND逻辑门。在DNA逻辑门的引导下，将纳米囊泡包裹的金碳量子点（gold carbon dots，GCD）送入靶细胞，通过GCD荧光的变化反映细胞内氧化还原状态的变化。总的来说，我们开发了DNA逻辑门控纳米囊泡，将不同的靶向因子收缩成靶细胞的独特标签。这种简单的功能化策略可以为构建智能纳米囊泡铺平道路，并将拓宽其在精准医学和个性化治疗领域的应用。
Engineering cell-derived nanovesicles with active-targeting ligands is an important strategy to enhance the targeting efficiency. However, the enhanced binding capability to targeting cells also leads to the binding with nontarget cells that share the same biomarkers. DNA-based logic gate is a kind of molecular system that responds to chemical inputs by generating output signals, and the relationship between the input and the output is based on a certain logic. Thus, the DNA-based logic gate could provide a new approach to improve the delivery efficiency of the nanovesicle. In this work, we developed a DNA logic-gated module that coupled two tumor cell-targeting factors (e.g., low pH and a tumor cell biomarker) in a Boolean manner. Immobilization of this module on the surface of the nanovesicle enables the nanovesicle to sense tumor cell-targeting factors and regard these cues as inputs AND logic gate. With the guide of DNA-based logic gate, gold carbon dots (GCDs) encapsulated within nanovesicles were delivered into target cells, and then the intracellular redox status variation was reflected by fluorescence change of GCDs. Overall, we developed DNA logic-gated nanovesicles that contract different targeting factors into a unique tag for target cells. This facile functionalization strategy can pave the way for constructing smart nanovesicles and would broaden their application in the field of precision medicine and personalized treatment.