Bimetallic oxide nanozyme-mediated depletion of glutathione to boost oxidative stress for combined nanocatalytic therapy.

Abstract

Although nanocatalytic therapy has become an emerging strategy for tumor treatment, the therapeutic effects of reactive oxygen species (ROS)-mediated treatment are still seriously limited by the inherent flaws of the enzymatic activities and the specific physicochemical properties of the tumor microenvironment (TME). Herein, we report an ultrasmall bimetallic oxide nanozyme (CuFe2O4@PEG, CFOs) for programmable multienzyme-like activities-primed combined therapy. Under the acidic condition, abundant highly toxic ROS can be generated through the peroxidase activity of CFOs with overexpressed hydrogen peroxide (H2O2) in the tumor. High metal ion utilization of bimetallic oxide nanozymes is related to the size effect and topological structure. Furthermore, glutathione peroxidase activity-initiated depletion of GSH disrupts the intracellular antioxidant defense system and further amplifies the oxidative stress in turn. Subsequently, oxygen generation originating from the catalase activity of CFOs relieves tumor hypoxia and achieves exceptional TME-customized therapeutic effects. Notably, the high photothermal effect (η = 41.12%) of CFOs in the second near-infrared biological windows leads to the combinational inhibition of tumor growth. In summary, this report provides a paradigm for the rational design of TME-responsive and ROS-mediated nanocatalytic treatment, which is promising for achieving superior therapeutic efficiency.

• Authors: Siyi Li, He Ding, Jinhu Chang, Shuming Dong, Boyang Shao, Yushan Dong, Shili Gai, Fei He, Piaoping Yang
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 623 Pg. 787-798 (Oct 2022) ISSN: 1095-7103 [Electronic] United States
• PMID: 35636288 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Oxides
• Reactive Oxygen Species
• Hydrogen Peroxide
• Glutathione

Topics

• Antioxidants
• Cell Line, Tumor
• Glutathione (metabolism)
• Humans
• Hydrogen Peroxide (chemistry)
• Neoplasms (drug therapy, pathology)
• Oxidative Stress
• Oxides (pharmacology)
• Reactive Oxygen Species
• Tumor Microenvironment