Extracellular Ion-Responsive Logic Sensors Utilizing DNA Dimeric Nanoassemblies on Cell Surface and Application to Boosting AS1411 Internalization
Extracellular Ion-Responsive Logic Sensors Utilizing DNA Dimeric Nanoassemblies on Cell Surface and Application to Boosting AS1411 Internalization
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利用细胞表面 DNA 二聚体纳米组件的细胞外离子响应逻辑传感器及其在促进 AS1411 内化中的应用
DOI：
10.1021/acs.analchem.0c01612
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Tao Li
中科院分区：
文献类型：
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作者：
Pai Peng;Qiwei Wang;Yi Du;Huihui Wang;Lili Shi;Tao Li
高水平的细胞外H+和K+是肿瘤微环境的独特特征，在癌症靶向药物输送方面显示出巨大的前景。在这里，我们利用细胞表面的原位二聚体骨架核酸(FNA)组装来设计H+和/或K+响应逻辑传感器，并首次将该逻辑传感器应用于在模拟肿瘤的细胞外环境中促进分子有效载荷的细胞内化。抗癌适配子AS1411被阻断在分枝的FNA顶点上，在那里双分子I-基序被拴住作为控制单元，以使二聚体DNA纳米组装能够响应细胞外pH的变化。K+促进AS1411折叠成G-四链，从而从二聚体FNA中释放出来，在二聚体FNA中发生基于邻近DNA杂交的FRET。此外，这种与门纳米传感器对AS1411内化的作用比传统途径更有效。这一发现对肿瘤微环境识别靶向药物输送和精确癌症治疗具有重要意义。
High levels of extracellular H+and K+are unique features of the tumor microenvironment and have shown great promise for use in cancer-targeted drug delivery. Here, we design H+- and/or K+-responsive logic sensors utilizing in situ dimeric framework nucleic acid (FNA) assembly on the cell surface and for the first time apply the logic sensors to boosting cellular internalization of molecular payloads in tumor-mimicking extracellular environments. An anticancer aptamer AS1411 is blocked on branched FNA vertexes where a bimolecular i-motif is tethered as the controlling unit to enable a dimeric DNA nanoassembly in response to extracellular pH change. K+promotes AS1411 to fold into a G-quadruplex and thereby release from dimeric FNA in which a proximity DNA hybridization-based FRET happens. Furthermore, such an AND-gated nanosensor functions more efficiently for AS1411 internalization than the conventional pathway. This finding shows significant implications for tumor-microenvironment-recognizing target drug delivery and precision cancer therapy.