Vicinal dithiol proteins-triggered prodrug activation: A novel strategy for Cancer-specific imaging and therapy

Theranostic platforms have garnered considerable attention as a promising strategy to enhance the precision and efficacy of cancer treatment. Vicinal dithiol proteins (VDPs) are critical for maintaining cellular redox balance, and their dysregulation is associated with various pathological conditions, such as cancer, stroke and neurodegenerative diseases. Herein, we design a novel VDPs-activated theranostic prodrug, Lena-green, which incorporates an α, β-unsaturated acrylamide group as a recognition site for the first time. Upon exposure to VDPs, Lena-green conjugates the fluorophore to VDPs while releasing lenalidomide (Lena), a clinically established anticancer drug, enabling fluorescence-based tracking and achieving high drug release efficiency in vitro. In murine models of subcutaneous breast cancer, Lena-green exhibited significantly enhanced therapeutic efficacy. This innovative design provides a promising strategy for real-time monitoring of drug release, thereby improving the precision and effectiveness of cancer treatment.