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Review
. 2025 Feb;20(3):279-290.
doi: 10.1080/17435889.2024.2446138. Epub 2024 Dec 27.

Nanozyme-mediated glutathione depletion for enhanced ROS-based cancer therapies: a comprehensive review

Xinyu Wang  1 , Nan Wei  2 , Yang Zhang  2 , Yuan Fang  2 , Yijun Li  3 , Songguo Li  3 , Zhanggui Wang  2 , Chenglong Sun  2   4
Affiliations
Review

Nanozyme-mediated glutathione depletion for enhanced ROS-based cancer therapies: a comprehensive review

Xinyu Wang et al. Nanomedicine (Lond). 2025 Feb.

Abstract

Nanozymes can improve reactive oxygen species (ROS)-based cancer therapies by targeting cancer cells' antioxidant defense mechanisms, particularly glutathione (GSH) depletion, to overcome ROS-resistant cancer cells. Nanozymes, innovative enzyme-mimetic nanomaterials, can generate ROS, alter the tumor microenvironment (TME), and synergize with photodynamic therapy (PDT), chemodynamic therapy (CDT), radiotherapy, and immunotherapy. This review shows how nanozymes catalyze ROS generation, selectively deplete GSH, and target cancer elimination, offering clear advantages over standard therapies. Nanozymes selectively target cancer cells' antioxidant defenses to improve PDT, CDT, and radiation therapies. To maximize nanozyme-based cancer treatment efficacy, biodistribution, biocompatibility, and tumor heterogeneity must be assessed. To improve cancer treatment, multifunctional, stimuli-responsive nanozymes and synergistic combination drugs should be developed.

Keywords: Nanozymes; multimodal cancer therapies; nanozymes glutathione depletion; reactive oxygen species (ROS); tumor microenvironment (TME).

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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