Selective Detection of Intracellular Drug Metabolism by Metal‐Organic Framework‐Coated Plasmonic Nanowire

Abstract

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.