A procedurally activatable nanoplatform for chemo/chemodynamic synergistic therapy.

Abstract

Responsive nano-drug delivery systems, especially multi-responsive systems, based on the complex characteristics of the tumor microenvironment (TME), such as acidic pH, hypoxia, and hydrogen peroxide (H2O2) overexpression, could enhance the biological activity of the drugs and reduce the side effects. In this study, a H2O2/glutathione (GSH) procedurally activatable nanoplatform (Cu9S5-PEG/DOX NSs) was prepared as a vector of drugs released by responsive morphologic transformation and the co-activated Fenton agent for tumor-specific synergistic therapy. After endocytosis into tumor cells, Cu9S5-PEG/DOX NSs were initially oxidized by over-expressed H2O2 and transformed from nanosheets to nanoflowers, leading to the release of doxorubicin (DOX). Subsequently, Cu9S5 nanoflowers (Cu9S5 NFs) reacted with the local GSH, liberated a large number of copper ions, and induced GSH depletion. The released DOX promoted the generation of intracellular H2O2 through cascade reactions, which were further utilized to facilitate the release of DOX and generate toxic hydroxyl radicals (˙OH) via a copper-based Fenton-like reaction. Cu9S5-PEG/DOX NSs sequentially activated by H2O2 and GSH in tumor cells exhibited relatively high cytotoxicity, whereas normal cells were still alive. This nanoplatform, as a procedurally activatable delivery system, may have excellent potential for tumor-specific synergistic therapy.

• Authors: Wen Han, Min Wang, Huaming He, Yifan Jiang, Chunhua Lu, Xiankun Tu
• Journal: Biomaterials science (Biomater Sci) Vol. 10 Issue 10 Pg. 2673-2680 (May 17 2022) ISSN: 2047-4849 [Electronic] England
• PMID: 35437541 (Publication Type: Journal Article)

Chemical References

• Copper
• Doxorubicin
• Hydrogen Peroxide
• Glutathione

Topics

• Cell Line, Tumor
• Copper (pharmacology)
• Doxorubicin (pharmacology, therapeutic use)
• Glutathione (pharmacology)
• Hydrogen Peroxide (pharmacology)
• Tumor Microenvironment