Azide-Locked Prodrug Co-Assembly into Nanoparticles with Indocyanine Green for Chemophotothermal Therapy

Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process. In this study, a hydrogen sulfide-responsive (H₂S) small molecule prodrug was synthesized by linking two chemotherapy drugs, camptothecin (CPT) and gemcitabine (GT), using a reductive disulfide bond simultaneously with a lock GT strategy using a H₂S-responsive azide group (denoted as N₃-GT-CPT). The ingenious design endows the easy coprecipitation peculiarity of the prodrug with clinical indocyanine green (ICG) via a combined interaction force of hydrophobic, π-π stacking, and electrostatic interactions of anions and cations, thus producing a more stable and multifunctional therapeutic nanosystem. Considering the great photothermal and imaging ability of ICG, the obtained nanosystem showed an excellent therapeutic ability against colon tumors in vitro and in vivo with selective response to intercellular H₂S, thus offering a good combination-based multiple therapy for treatment of tumors.