Engineering a highly tumor microenvironment-responsive nanoplatform toward effective chemotherapy has always been a challenge in targeted cancer treatment. Metal-organic frameworks are a promising delivery system to reformulate previously approved drugs for enhanced chemotherapy, such as disulfiram (DSF). Herein, a tumor microenvironment-activated metal-organic framework–based nanoplatform DSF@MOF-199@FA has been fabricated to realize amplified oxidative stress–induced enhanced chemotherapy. Our results unveil that the copper ions and DSF released by DSF@MOF-199@FA in an acidic environment can be converted into toxic bis(N, N-diethyl dithiocarbamate) copper and then induce cell apoptosis. Simultaneously, we determined that the apoptosis outcome is further promoted by amplified oxidative stress through effective generation of reactive oxygen species and GSH elimination. In conclusion, this work provides a promising platform for effective anticancer treatment.

设计一个对肿瘤微环境高度敏感的纳米平台以实现有效的化疗一直是靶向癌症治疗中的一个挑战。金属有机框架是一种很有前途的递送系统，可以重新配制先前批准的增强化疗药物，例如双硫仑 (DSF)。在此，构建了一种基于肿瘤微环境激活的金属有机框架的纳米平台DSF@MOF-199@FA，以实现放大的氧化应激诱导的增强化疗。我们的结果表明， DSF@MOF-199@FA释放的铜离子和 DSF在酸性环境中可转化为有毒的双（N，N-二乙基二硫代氨基甲酸）铜，进而诱导细胞凋亡。同时，我们确定通过有效产生活性氧和消除 GSH，放大的氧化应激进一步促进细胞凋亡结果。总之，这项工作为有效的抗癌治疗提供了一个有前途的平台。