効率的ドラッグデリバリーシステム構築へ向けたナノ・プロドラッグの細胞内動態の解明に関する研究

Tohoku University笠井均課

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

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

Liquid-phase photo-induced covalent modification (PICM) of single-layer graphene by short-chain fatty acids

We report an efficient photo-induced covalent modification (PICM) of graphene by short-chain fatty acids (SCFAs) with an alkyl chain at the liquid-solid interface for spatially resolved chemical functionalization of graphene. Light irradiation on monolayer graphene under an aqueous solution of the SCFAs with an alkyl chain efficiently introduces sp(3)-hybridized defects, where the reaction rates of PICM are significantly higher than those in pure water. Raman and IR spectroscopy revealed that a high density of methyl, methoxy, and acetate groups is covalently attached to the graphene surface while it was partially oxidized by other oxygen-containing functional groups, such as OH and COOH. A greater downshift of the G-band in Raman spectra was observed upon the PICM with longer alkyl chains, suggesting that the charge doping effect can be controlled by the alkyl chain length of the SCFAs. The systematic research and exploration of covalent modification in SCFAs provide new insight and a potentially facile method for bandgap engineering of graphene