Article ; Online: Glutathione/pH-responsive copper-based nanoplatform for amplified chemodynamic therapy through synergistic cycling regeneration of reactive oxygen species and dual glutathione depletion
Journal of Colloid And Interface Science. 2023 Aug. 07,
2023
Abstract: The rapid scavenging of reactive oxygen species (ROS) by glutathione (GSH) and insufficient endogenous hydrogen peroxide (H₂O₂) in tumor cells are the major factors greatly restricting the efficacy of chemodynamic therapy (CDT). Herein, we developed a ... ...
| Abstract | The rapid scavenging of reactive oxygen species (ROS) by glutathione (GSH) and insufficient endogenous hydrogen peroxide (H₂O₂) in tumor cells are the major factors greatly restricting the efficacy of chemodynamic therapy (CDT). Herein, we developed a tumor microenvironment (TME)-responsive Cu-based metal-mesoporous organosilica nanoplatform integrating vitamin k3 (VK3), which could deplete GSH and specifically regenerate H₂O₂ for amplified CDT cancer therapy. Once the CuO@MON-PEG/VK3 nanoparticles entered into the tumor cells through enhanced permeability and retention (EPR) effect, the organosilicon shell and CuO core would be successively degraded upon the triggering of GSH and endo/lysosomal acidity. Subsequently, the enriched tetrasulfide bridges and released Cu²⁺ could consume GSH substantially, thus triggering Fenton-like reaction for CDT. Furthermore, the released VK3 could be catalyzed by the highly expressed quinone oxidoreductase-1 (NQO1) inside tumor cells to generate sufficient H₂O₂ through a “reversible” redox cycle, which in turn promoted Cu⁺-mediated Fenton-like reaction. Both in vitro and in vivo studies demonstrated that this nanoplatform could achieve synergistic CDT therapy against tumor through synergistic cycling regeneration of ROS and dual GSH exhaustion with excellent biosafety. Our finding highlight the promising potential of CuO@MON-PEG/VK3 nanoplatform with multiple oxidative stress amplification for highly efficient tumor therapy. |
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| Keywords | acidity ; biosafety ; cancer therapy ; copper ; glutathione ; hydrogen peroxide ; menadione ; nanoparticles ; neoplasms ; organosilicon compounds ; oxidative stress ; permeability ; Tumor microenvironment ; Chemodynamic therapy ; Reactive oxygen species |
| Language | English |
| Dates of publication | 2023-0807 |
| Publishing place | Elsevier Inc. |
| Document type | Article ; Online |
| Note | Pre-press version |
| ZDB-ID | 241597-5 |
| ISSN | 1095-7103 ; 0021-9797 |
| ISSN (online) | 1095-7103 |
| ISSN | 0021-9797 |
| DOI | 10.1016/j.jcis.2023.08.043 |
| Database | NAL-Catalogue (AGRICOLA) |
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