Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD-L1 for Enhanced Cancer Immunotherapy
© 2023 Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 22 vom: 07. Juni, Seite e2212267 |
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| Weitere Verfasser: | , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article cuproptosis immunotherapy nanoparticles tumor microenvironment elesclomol 6UK191M53P Copper 789U1901C5 Reactive Oxygen Species |
| Zusammenfassung: | © 2023 Wiley-VCH GmbH. Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces cell death. However, existing Cu ionophores are small molecules with a short blood half-life making it hard to transport enough Cu into cancer cells. Herein, a reactive oxygen species (ROS)-sensitive polymer (PHPM) is designed, which is used to co-encapsulate elesclomol (ES) and Cu to form nanoparticles (NPESCu). After entering cancer cells, ES and Cu, triggered by excessive intracellular ROS, are readily released. ES and Cu work in a concerted way to not only kill cancer cells by cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu to efficiently transport Cu and induce cuproptosis is investigated. In addition, the change in the transcriptomes of cancer cells treated with NP@ESCu is explored by RNA-Seq. In vivo, NP@ESCu is found to induce cuproptosis in the mice model with subcutaneous bladder cancer, reprograming the tumor microenvironment. Additionally, NP@ESCu is further combined with anti-programmed cell death protein ligand-1 antibody (αPD-L1). This study provides the first report of combining nanomedicine that can induce cuproptosis with αPD-L1 for enhanced cancer therapy, thereby providing a novel strategy for future cancer therapy |
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| Beschreibung: | Date Completed 02.06.2023 Date Revised 02.06.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202212267 |