【摘要】 本文报道了一种基于二茂铁与苯并硒二唑（SeNBD）偶联物的前药FcNH-SeNBD，用于肿瘤细胞化学动力学治疗（CDT）与荧光成像。FcNH-SeNBD利用肿瘤细胞中过表达的过氧化氢（H₂O₂）氧化二茂铁发生芬顿反应，高效生成羟基自由基（·OH），诱导肿瘤细胞凋亡。与此同时，二茂铁的氧化阻断了其与苯并硒二唑之间的光致电子转移（PET）效应，使得原本被猝灭的SeNBD荧光得以恢复，实现了荧光信号“Off-On”的转变，用于实时监测前药在肿瘤细胞中的活化与富集，便于治疗效果的预测与评估。体外实验表明FcNH-SeNBD对肝癌细胞HepG2[IC₅₀=（7.95±0.98）μg·mL^-1]和结直肠癌细胞HCT116[IC₅₀=（15.74±1.5）μg·mL^-1]具有显著的选择性杀伤作用，而对正常结肠上皮细胞NCM-460无显著毒性(IC₅₀>100μg·mL^-1)。机制研究证实，FcNHSeNBD通过激活caspase-3依赖性凋亡通路发挥对肿瘤细胞的杀伤作用。细胞成像实验表明FcNH-SeNBD可在肿瘤细胞中富集并产生强烈的红色荧光。更多还原

【Abstract】 This article reports the rational design of a chemodynamic prodrug,FcNH-SeNBD.The prodrug was constructed by coupling ferrocene with benzoselenadiazole（SeNBD）.By taking advantage of the elevated level of H₂O₂in cancer cells,FcNH-SeNBD could generate cytotoxic ·OH radicals to induce cancer cell apoptosis and remain non-toxic in normal cells.In the meantime,the oxidation of ferrocene may interrupt its photo-induced electron transfer to SeNBD and facilitate the fluorescence recovery,thereby enabling FcNH-SeNBD for cancer cell imaging.FcNH-SeNBD was cytotoxic against liver cancer cell line HepG2 [IC₅₀=（7.95±0.98） μg·mL^-1] and colon cancer cell line HCT116 [IC₅₀=（15.74±1.5） μg·mL^-1],while displayed minimum toxicity to normal epithelial colonic cell line NCM-460(IC₅₀>100 μg·mL^-1),demonstrating its selective toxicity to cancer cell line.Mechanistic investigations revealed that FcNH-SeNBD was able to induce cancer cell apoptosis through caspase-3-dependent pathways.Moreover,a cell imaging study confirmed the strong red fluorescence signal of FcNH-SeNBD upon internalization and subsequent activation in tumor cells.更多还原