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经特洛伊木马载体递送球形核酸探针进入细胞质,实现 microRNAs 的高保真成像。

Trojan Horse Delivery of Spherical Nucleic Acid Probes into the Cytoplasm for High-Fidelity Imaging of MicroRNAs.

机构信息

Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China.

State Key Laboratory of Medicinal Chemical Biology, Research Center for Analytical Sciences, and Tianjin Key Laboratory of Molecular Recognition and Biosensing, College of Chemistry, Nankai University, Tianjin 300071, China.

出版信息

Anal Chem. 2022 Aug 9;94(31):10942-10948. doi: 10.1021/acs.analchem.2c00675. Epub 2022 Jul 19.

DOI:10.1021/acs.analchem.2c00675
PMID:35854635
Abstract

We report a Trojan horse strategy to efficiently deliver the spherical nucleic acid probes (namely, nanoflares) into the cytoplasm for microRNA (miRNA) imaging with high fidelity, breaking through the cytoplasmic transport dilemma of RNA probes in living cells. The nanoflare is encapsulated into a "Trojan horse" consisting of zwitterionic choline phosphates (CPs) and acid-degradable crosslinkers; the former effectively promotes cell uptake and the latter triggers instantaneous liberation of the nanoflare probes from the lysosome to the cytoplasm. The exposed nanoflares in the cytoplasm can be lightened up by the target miRNAs specifically. Compared with the conventional nanoflares as well as the improved ones in previous reports, the "Trojan horse" nanoflares avoid nuclease degradation and thiol displacement during the delivery process, providing unprecedentedly high accuracy for intracellular miRNA imaging.

摘要

我们报告了一种特洛伊木马策略,可有效地将球形核酸探针(即纳米耀斑)递送至细胞质中,以实现高保真度的 microRNA(miRNA)成像,从而突破了 RNA 探针在活细胞中细胞质转运的困境。纳米耀斑被封装在由两性离子胆碱磷酸盐(CPs)和酸可降解交联剂组成的“特洛伊木马”中;前者可有效促进细胞摄取,后者则触发纳米耀斑探针从溶酶体到细胞质的瞬时释放。细胞质中暴露的纳米耀斑可以被靶标 miRNA 特异性点亮。与传统的纳米耀斑以及之前报道中的改进型纳米耀斑相比,“特洛伊木马”纳米耀斑在递送过程中避免了核酸酶降解和巯基置换,为细胞内 miRNA 成像提供了前所未有的准确性。

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