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Mitochondria MicroRNA Spatial Imaging via pH-Responsive Exonuclease-Assisted AIE Nanoreporter
Analytical Chemistry ( IF 6.7 ) Pub Date : 2022-07-18 , DOI: 10.1021/acs.analchem.2c00941
Jinya Du 1 , Yuchun Qiao 1 , Xiangdan Meng 1 , Wei Wei 1 , Wenhao Dai 1 , Lingzhi Yang 2 , Changying Yang 3 , Haifeng Dong 1, 2
Affiliation  

Mitochondrial microRNAs (mitomiRs) critically orchestrate mitochondrial functions. Spatial imaging of mitomiRs is essential to understand its clinical value in diagnosis and prognosis. However, the direct monitoring of mitomiRs in living cells remains a key challenge. Herein, we report an AIE nanoreporter strategy for mitomiRs imaging in living cells through pH-controlled exonuclease (Exo)-assisted target cycle signal amplification. The AIE-labeled DNA detection probes are conjugated on Exo III encapsulated polymeric nanoparticles (NPs) via consecutive adenines (polyA). The amplified sensing functions are off during the cytoplasm delivery process, and it can be spatially switched from off to on when in the alkaline mitochondria (about pH 8) after triphenylphosphonium (TPP)-mediated mitochondrial targeting. Where the NPs degraded to release Exo III and cancer-specific mitomiRs hybridize with AIE-labeled DNA detection probes to expose the cleavage site of released Exo III, enabling spatially restricted mitomiRs imaging. The mitomiRs expression fluctuation was also realized. This study contributes to a facile strategy that could easily extend to a broad application for the understanding of mitomiRs-related pathological processes.

中文翻译:

通过 pH 响应外切酶辅助 AIE Nanoreporter 的线粒体 MicroRNA 空间成像

线粒体 microRNA (mitomiRs) 严格协调线粒体功能。有丝分裂的空间成像对于了解其在诊断和预后中的临床价值至关重要。然而,直接监测活细胞中的 mitomiRs 仍然是一个关键挑战。在这里,我们报告了一种 AIE 纳米报告策略,用于通过 pH 控制的核酸外切酶 (Exo) 辅助靶循环信号放大在活细胞中进行 mitomiRs 成像。AIE 标记的 DNA 检测探针通过连续的腺嘌呤 (polyA) 与 Exo III 封装的聚合物纳米颗粒 (NP) 结合。放大的传感功能在细胞质递送过程中关闭,并且在三苯基鏻 (TPP) 介导的线粒体靶向后,在碱性线粒体(约 pH 8)中,它可以在空间上从关闭切换到开启。当 NPs 降解以释放 Exo III 时,癌症特异性 mitomiRs 与 AIE 标记的 DNA 检测探针杂交以暴露释放的 Exo III 的切割位点,从而实现空间受限的 mitomiRs 成像。也实现了mitomirs表达波动。这项研究有助于一种简单的策略,可以很容易地扩展到广泛的应用,以了解与 mitomiRs 相关的病理过程。
更新日期:2022-07-18
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