Theranostic Heterodimeric Prodrug with Dual-Channel Fluorescence Turn-On and Dual-Prodrug Activation for Synergistic Cancer Therapy.

Abstract

Theranostic prodrugs that can precisely monitor drug activation with synergistic therapeutic effects are highly desirable for personalized medicine. In this study, a theranostic heterodimeric prodrug, CyNH-SS-DOX, with synchronous and independent dual-channel fluorescence turn-on and dual-prodrug activation for synergistic cancer therapy is developed. A hemicyanine fluorescent drug, CyNH₂ , with good therapeutic effects found in this work, is conjugated to doxorubicin (DOX) through a disulfide linker to form CyNH-SS-DOX. Before activation, both the fluorescence of DOX and CyNH₂ are in the off state and the toxicity is low. In the presence of intracellular glutathione, both the fluorescence of DOX and CyNH₂ at different channels are turned on. Meanwhile, DOX and CyNH₂ are activated in a synergistic anticancer effect. It is believed that CyNH-SS-DOX is promising for monitoring prodrug activation in dual-fluorescence channels and for enhancing therapeutic efficacy with few side effects.