Highly specific GSH-triggered bifunctional molecules to enable precise imaging and targeted therapy of cancer.

The utilization of diagnostic-integrated molecules can enable targeted delivery and controlled release to significantly enhance therapeutic effectiveness and minimize toxic effects. Herein, we developed a novel class of glutathione (GSH)-activated bifunctional molecules that respond to elevated levels of GSH in tumor microenvironment. These bifunctional molecules retained the pharmacodynamic effects of parent molecules and mitigated cytotoxicity. Meanwhile, controlled release was monitored using fluorescent signals, enabling detection of drug distribution and accumulation in situ and in real time. Moreover, the correlation between GSH levels and fluorescence intensity offers the possibility of monitoring the effectiveness of responsive drugs. In conclusion, bifunctional molecules, as novel diagnostic-integrated molecules with both fluorescence imaging and therapeutic effects, exhibited potential applications in cancer therapy and imaging.