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 N-3-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, pi-pi 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.

Automated summary

In this study, a stable and multifunctional therapeutic nanosystem was successfully fabricated using a hydrogen sulfide-responsive small molecule prodrug. The nanosystem exhibited excellent photothermal and imaging abilities and showed remarkable therapeutic efficacy against colon tumors in vitro and in vivo. By selectively responding to intercellular H2S, the nanosystem offers the potential for combination-based multiple therapy for tumor treatment.