Formulation of DOX-dimer with bi-functionalized chitooligosaccharide for tumor-specific self-boosted drug release and synergistic chemo/chemodynamic therapy

The toxic side effects and possible drug resistance of the chemotherapeutics hinder their antitumor efficacy. Here, a pH/reactive oxygen species (ROS) dual-triggered nanodrug was developed for the tumor-specific self-boosted drug release and synergistic chemo/chemodynamic therapy, by formulating ROS-cleavable doxorubicin (DOX)-based dimer (DOX-TK-DOX) with bi-functionalized chitooligosaccharide (COS-Fc-TK) with ferrocenecarboxylic acid (Fc) and thioketal (TK). The resultant DOX-TK-DOX/COS-Fc-TK nanoparticles with a high DOX content of 39.70 % showed tumor-specific self-boosted drug release, which was triggered by highly toxic OH generated via Fc-catalyzed Fenton reaction of the endogenous H2O2 in tumor intracellular microenvironment. As a result, a synergistic chemo/chemodynamic therapy with combination index (CI) of 0.94 was achieved for selective treatment of tumors.