期刊
CHEMICAL ENGINEERING JOURNAL
卷 435, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2022.135083
关键词
Fenton reaction; Tumor microenvironment; Nanoenzyme; Chemodynamic therapy; Sonodynamic therapy
资金
- National Natural Science Foundation of China [21904010, 21875008, 51773017]
- Excellent Young Scientists Fund [22022407]
- Fundamental Research Funds for the Central Universities [FRF-TP-19-021A1, FRF-BR-20-03B]
In this study, a novel Cu-CuFe2O4 nanoenzyme was developed for simultaneous relief of hypoxia and depletion of GSH, enhancing the therapeutic effect of ROS-involved therapy. The nanoenzyme exhibited catalytic activities to continuously generate oxygen from tumor-overexpressed hydrogen peroxide, facilitating hypoxia-relieved sonodynamic therapy. Additionally, the Cu-CuFe2O4 NPs reacted with GSH to generate abundant hydroxyl radicals for chemodynamic therapy. The efficient anticancer ability of Cu-CuFe2O4 NPs was demonstrated in MCF-7 cell killing and multicellular tumor spheroids elimination.
Specific hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME) are bottleneck for reactive oxygen species (ROS)-involved therapy performance. Herein, we report a novel Cu-CuFe2O4 nanoenzyme enables simultaneous hypoxia relief and GSH depletion for efficiently augmenting ROS-involved chemodynamic (CDT)/sonodynamic (SDT) therapy. The nanoenzyme exhibited both catalase-like and GSH peroxidase-like catalytic activities, which can persistently catalyze tumor-overexpressed hydrogen peroxide (H2O2) to generate oxygen (O-2) to facilitate singlet oxygen (O-1(2)) production under an external ultrasound, achieving hypoxia-relieved SDT. Meanwhile, the Cu-CuFe2O4 NPs reacted with GSH to deplete GSH and release Fenton-like Cu+ and Fe2+ ions to mediate abundant hydroxyl radical ((OH)-O-center dot) production for CDT. Highly efficient anticancer ability of the Cu-CuFe2O4 NPs was demonstrated from the efficient MCF-7 cells killing and multicellular tumor spheroids (MCTS) elimination. This work provides a useful strategy to design multi-mode TME-responsive nanosonosensitizer for enhancing therapeutic effect of cancer therapy via persistent and simultaneous regulatory of TME, showing a great potential for clinical cancer therapy.
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