Activating Two-Photon Silica Nanoamplifier-Based CHA and FRET for Accurate Ratiometric Bioimaging of Intracellular MicroRNA

作者：Kangdi He, Zhen Cheng, Xianmiao Zhang, Zhiling Qian, Jia Chen, Bingqian Li, Fa‐Yan Meng, Shengrong Yu, Keqi Tang, Yong‐Xiang Wu · 发表于：Analytical Chemistry · 年份：2024 · DOI：10.1021/acs.analchem.4c03630 · 被引用次数：13 · 研究领域：Advanced biosensing and bioanalysis techniques、Analytical Chemistry and Sensors、RNA Interference and Gene Delivery

In situ visualization of microRNA (miRNA) in cancer cells and diseased tissues is essential for advancing our comprehension of the onset and progression of associated diseases. Two-photon (TP) imaging, as an imaging technology with high spatiotemporal resolution, deep tissue penetration, and accurate target quantification, has distinctive advantages over single-photon imaging and has attracted increasing attention. Extensive research has been conducted on two-photon dye-doped silica nanoparticles, which exhibit a large two-photon absorption (TPA) cross-section, high fluorescence quantum yield, and excellent biocompatibility. However, the low abundance of RNA in tumor cells leads to insufficient signal output. Based on functional nucleic acid, a catalyzed hairpin self-assembly (CHA) signal amplification strategy, which has simplicity, robustness, and nonenzymatic characteristics, can achieve the amplification of DNA or RNA signals. Here, a two-photon silica nanoamplifier (TP-SNA) utilizing TP dye-doped silica nanoparticles (SiNPs) and functional nucleic acid was constructed, employing triggering catalyzed hairpin self-assembly and fluorescence resonance energy transfer (FRET) for highly sensitive detection and precise TP imaging of endogenous miRNAs in tumor cells and tissues at varying depths. The TP-SNA demonstrated the capability to detect miR-203 with a detection limit of 33 pM. The maximum two-photon tissue penetration depth of the two-photon nanoamplifier was 210 μm. The...