Logic Nanodevice-Mediated Receptor Assembly for Nongenetic Regulation of Cell Behavior in Tumor-like Microenvironment,Nano Letters

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Logic Nanodevice-Mediated Receptor Assembly for Nongenetic Regulation of Cell Behavior in Tumor-like Microenvironment
Nano Letters ( IF 9.6 ) Pub Date : 2023-02-24 , DOI: 10.1021/acs.nanolett.2c04657
Yuchen Wu ₁ , Jin Huang ₁ , Hui He ₁ , Meixia Wang ₁ , Guanyu Yin ₁ , Lanlin Qi ₁ , Xiaoxiao He ₁ , Hong-Hui Wang ₁ , Kemin Wang ₁

Affiliation

The reprogramming of cell signaling and behavior through the artificial control of cell surface receptor oligomerization shows great promise in biomedical research and cell-based therapy. However, it remains challenging to achieve combinatorial recognition in a complicated environment and logical regulation of receptors for desirable cellular behavior. Herein, we develop a logic-gated DNA nanodevice with responsiveness to multiple environmental inputs for logically controlled assembly of heterogeneous receptors to modulate signaling. The “AND” gate nanodevice uses an i-motif and an ATP-binding aptamer as environmental cue-responsive units, which can successfully implement a logic operation to manipulate receptors on the cell surface. In the presence of both protons and ATP, the DNA nanodevice is activated to selectively assemble MET and CD71, which modulate the HGF/MET signaling, resulting in cytoskeletal reorganization to inhibit cancer cell motility in a tumor-like microenvironment. Our strategy would be highly promising for precision therapeutics, including controlled drug release and cancer treatment.

中文翻译：

逻辑纳米器件介导的受体组装用于肿瘤样微环境中细胞行为的非遗传调控

通过人工控制细胞表面受体寡聚化来重新编程细胞信号和行为，在生物医学研究和基于细胞的治疗中显示出巨大的前景。然而，在复杂的环境中实现组合识别和对理想细胞行为的受体进行逻辑调节仍然具有挑战性。在此，我们开发了一种逻辑门控 DNA 纳米器件，它对多种环境输入具有响应性，用于逻辑控制异质受体的组装以调节信号。“与”门纳米器件使用一个 i-motif 和一个 ATP 结合适体作为环境提示响应单元，可以成功地实现逻辑运算来操纵细胞表面的受体。在质子和 ATP 存在的情况下，DNA 纳米装置被激活以选择性地组装 MET 和 CD71，其调节 HGF/MET 信号，导致细胞骨架重组以抑制癌细胞在肿瘤样微环境中的运动。我们的策略对于精准治疗非常有前途，包括控制药物释放和癌症治疗。

更新日期：2023-02-24

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