Redox-Activatable Theranostic Co-Prodrug for Precise Tumor Diagnosis and Selective Combination Chemotherapy

A novel theranostic co-prodrug SCB has been
designed
by combining a co-prodrug from CDDO-Me and SAHA with a biotin-coupled
near-infrared (NIR) probe hemicyanine via redox-responsive linker
thiolactate to enhance the tumor theranostic efficacy and reduce the
toxic side effects using both active and passive targeting strategies. SCB displayed reactive oxygen species (ROS)- and glutathione
(GSH)-dependent release of NIR fluorescence and two parent drugs.
Furthermore, the administration of SCB caused selective
illumination of the tumor tissues for >24 h, thereby guiding precise
removal of a tumor from intraoperative mice. Importantly, SCB exhibited highly efficient tumor inhibition, exerted selective combination
therapy through prodrug mode, and minimized the adverse effects. Finally, SCB induced mitochondrial depolarization, DNA damage, and
cell apoptosis through ROS generation and downregulation of HDAC6
protein, as verified by H2AX, Bax, cleaved-PARP, and Mcl-1 proteins.
Thus, we suggest that SCB can provide a new platform
for both precise diagnosis-guided tumor removal and selective combination
therapy with high safety.