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(H_(2)O_(2))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[IC_(50)=(7.95±0.98)μg·mL^(-1)]和结直肠癌细胞HCT116[IC_(50)=(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(IC_(50)>100μg·mL^(-1))。机制研究证实,FcNH-SeNBD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。
This article reports the rational design of a chemodynamic prodrug,FcNH-SeNBD.The prodrug was con-structed by coupling ferrocene with benzoselenadiazole(SeNBD).By taking advantage of the elevated level of H_(2)O_(2)in 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 trans-fer 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[IC_(50)=(7.95±0.98)μg·mL^(-1)]and colon cancer cell line HCT116[IC_(50)=(15.74±1.5)μg·mL^(-1)],while displayed minimum toxicity to normal epithelial colonic cell line NCM-460(IC_(50)>100μg·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.More-over,a cell imaging study confirmed the strong red fluorescence signal of FcNH-SeNBD upon internalization and subsequent activation in tumor cells.
作者
徐基超
胡明
陈希昌
王春辉
王磊晨
周玲伊
何星
程夏民
景苏
XU Jichao;HU Ming;CHEN Xichang;WANG Chunhui;WANG Leichen;ZHOU Lingyi;HE Xing;CHENG Xiamin;JING Su(School of Chemistry and Molecular Engineering,Nanjing Tech University,Nanjing 211816,China)
出处
《无机化学学报》
北大核心
2025年第8期1495-1504,共10页
Chinese Journal of Inorganic Chemistry
基金
国家自然科学基金(No.22175090)
南京工业大学化学拔尖基地本科生科研探索基金(No.FTBR2405)资助。
关键词
二茂铁
苯并硒二唑
前药
化学动力学治疗
荧光成像
ferrocene
benzoselenadiazole
prodrug
chemodynamic therapy
fluorescence imaging
作者简介
通信联系人:景苏。E-mail:sjing@njtech.edu.cn。
