Selective Detection of Intracellular Drug Metabolism by Metal‐Organic Framework‐Coated Plasmonic Nanowire
Selective Detection of Intracellular Drug Metabolism by Metal‐Organic Framework‐Coated Plasmonic Nanowire
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DOI：
10.1002/adom.202300856
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发表时间：
2023-05
影响因子：
9
通讯作者：
Qian Zhang;Taku Murasugi;Kotomi Watanabe;Han Wen;Ya Tian;M. Ricci;S. Rocha;T. Inose;H. Ka
中科院分区：
文献类型：
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作者：
Qian Zhang;Taku Murasugi;Kotomi Watanabe;Han Wen;Ya Tian;M. Ricci;S. Rocha;T. Inose;H. Ka
揭示细胞内药物代谢对于改善药物开发至关重要，这需要在细胞内环境中进行具有分子选择性的实时检测。使用金属纳米颗粒的表面增强拉曼散射 (SERS) 可以检测活细胞中的分子，但进入细胞后，大多数纳米颗粒被捕获到囊泡中，限制了这些室内的 SERS 检测。此外，由于内源性物质的拉曼指纹干扰药物信号，在复杂的细胞内环境中识别目标信号具有挑战性。为了克服这些问题，本文报道了带有沸石咪唑酯骨架-8（ZIF-8）的银纳米线涂层作为一种具有分子选择性的新型内窥镜探针，用于研究常见抗癌药物伊立替康在细胞中的位置和代谢。细胞中的伊立替康被羧酸酯酶代谢形成 SN-38，抑制拓扑异构酶 I 和 DNA 合成。由于 ZIF-8 的分子选择性，内窥镜探针比伊立替康选择性地吸附和检测 SN-38 的 SERS 信号。这种选择性能够监测伊立替康向 SN-38 的转化，并随时间跟踪其在细胞内的位置。这项工作清楚地表明了金属有机框架涂层纳米线内窥镜在特异性跟踪药物分子并探索其在细胞中的代谢方面的潜力。
Unveiling intracellular drug metabolism is crucial for improving drug development, which requires real‐time detection with molecular selectivity in the intracellular environment. Surface‐enhanced Raman scattering (SERS) with metal nanoparticles enables the detection of molecules in living cells, but after entering the cells, most nanoparticles are captured into vesicles, limiting the SERS detection inside these compartments. Moreover, the identification of the target signal in the complex intracellular environment is challenging due to Raman fingerprints from endogenous material interfering with the drug signal. To overcome these issues, here the coating of a silver nanowire with zeolitic imidazolate framework‐8 (ZIF‐8) as a novel endoscopic probe with molecular selectivity to investigate the location and metabolism in cells of a common anticancer drug, irinotecan, is reported. Irinotecan in cells is metabolized by carboxylesterase to form SN‐38, which inhibits topoisomerase I and DNA synthesis. Thanks to the molecular selectivity of ZIF‐8, the endoscopic probe selectively adsorbs and detects SERS signal of SN‐38 over irinotecan. This selectivity enables monitoring of the conversion of irinotecan into SN‐38 and following its intracellular location over time. This work clearly shows the potential of metal‐organic framework‐coated nanowire endoscopy to specifically track drug molecules and explore their metabolism in cells.