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

Abstract

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.

• Authors: Pengwei Xie, Peng Liu
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 320 Pg. 121210 (Nov 15 2023) ISSN: 1879-1344 [Electronic] England
• PMID: 37659811 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

Chemical References

• oligochitosan
• Hydrogen Peroxide
• Reactive Oxygen Species
• ferrocenecarboxylic acid
• Chitin
• Doxorubicin
• Polymers

Topics

• Humans
• Drug Liberation
• Hydrogen Peroxide
• Reactive Oxygen Species
• Neoplasms
• Chitin
• Doxorubicin (pharmacology, therapeutic use)
• Polymers
• Tumor Microenvironment