Chlorambucil combined with a fluorophore for targeted cancer therapy and real-time monitoring of cancer cell death

Abstract

The clinical applications of chlorambucil are limited by poor cellular permeability, lack of targeting, and severe side effects. In this study, a novel fluorophore-drug conjugate using chlorambucil as a model anticancer agent and 1,8-naphthalimide derivatives as the parent fluorophore was constructed. This novel fluorophore-drug conjugate could maintain a high concentration and high toxicity of drug in cancer cells by targeting lipid droplets. Cell imaging showed that the constructed novel fluorophore-drug conjugate exhibited a good cell uptake ability. Furthermore, the fluorophore component of conjugate acted as a fluorescent dye that emitted measurable signal when interacting with cancer cells. Therefore, fluorophore-drug conjugate showed the potential to be used for monitoring drug biodistribution in vivo in real time, which was of great significance in studying the mechanism of action of anticancer agents. Finally, we estimated of cancer cell death by monitoring the decrease in the number of lipid droplets and the increase in cell polarity. In conclusion, a novel fluorophore-drug conjugate with high cancer cell toxicity and capable of real-time monitoring of cancer cell survival status was successfully developed,opening up new possibilities for cancer therapy and diagnosis.