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

• Published in: Carbohydrate polymers Vol. 320; p. 121210
• Main Authors: Xie, Pengwei, Liu, Peng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 15.11.2023
• Subjects: Functionalized chitooligosaccharide; pH/ROS dual-triggered; ROS-activated DOX-based dimer; Self-boosted drug release; Synergistic chemo/chemodynamic therapy; Synergistic chemo/chemodynamic therapy; ROS-activated DOX-based dimer; Self-boosted drug release; pH/ROS dual-triggered; Functionalized chitooligosaccharide
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2023.121210

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. [Display omitted]