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Glutathione-Responsive Biodegradable Core–Shell Nanoparticles That Self-Generate H2O2 and Deliver Doxorubicin for Chemo–Chemodynamic Therapy.

Authors :
Liu, Ying
Chi, Siyu
Cao, Yu
Liu, Zhihong
Source :
ACS Applied Nano Materials; 2/25/2022, Vol. 5 Issue 2, p2592-2602, 11p
Publication Year :
2022

Abstract

As a kind of reactive oxygen species (ROS)-mediated cancer therapy modality, chemodynamic therapy (CDT) has been extensively explored. However, the insufficient endogenous H<subscript>2</subscript>O<subscript>2</subscript> and the intracellular redox homeostasis greatly obstruct the anticancer efficacy. Developing multifunctional nanomedicine which can address these issues is appealing. Herein, 4T1 cancer cell membrane (CM)-coated glutathione (GSH)-responsive biodegradable biomimetic nanoreactor, CaO<subscript>2</subscript>@MnO<subscript>2</subscript>–DOX@CM, was fabricated for tumor oxidative stress amplification enhanced self-supplying H<subscript>2</subscript>O<subscript>2</subscript> chemodynamic therapy and synergistic chemotherapy. Highly expressed GSH in the tumor cells could trigger the biodegradation of CaO<subscript>2</subscript>@MnO<subscript>2</subscript>–DOX@CM, and the Fenton-like catalyst Mn<superscript>2+</superscript> and chemotherapy drug doxorubicin (DOX) were released. The unprotected CaO<subscript>2</subscript> further reacted with water to generate a large amount of H<subscript>2</subscript>O<subscript>2</subscript> and Ca<superscript>2+</superscript>. The self-supplying H<subscript>2</subscript>O<subscript>2</subscript> not only reacted with Mn<superscript>2+</superscript> to generate hydroxyl radical (<superscript>•</superscript>OH) but also sped up the biodegradation of the nanoreactor. Furthermore, the MnO<subscript>2</subscript>-mediated GSH depletion and the Ca<superscript>2+</superscript>-overloading-induced mitochondria dysfunction could further enhance the CDT efficiency. Thus, the glutathione-responsive biodegradable core–shell nanoparticles achieved MRI-guided synergistic chemo–chemodynamic therapy, showing bright prospect for highly efficient tumor treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
25740970
Volume :
5
Issue :
2
Database :
Complementary Index
Journal :
ACS Applied Nano Materials
Publication Type :
Academic Journal
Accession number :
155959819
Full Text :
https://doi.org/10.1021/acsanm.1c04277