Multifunctional Copper-Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy
© 2024 Wiley‐VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 45 vom: 16. Nov., Seite e2409066 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
|
| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article Cuproptosis immunotherapy metal‐phenolic polyamines depletion pyroptosis Copper 789U1901C5 Polyamines Reactive Oxygen Species |
| Zusammenfassung: | © 2024 Wiley‐VCH GmbH. The overexpression of polyamines in tumor cells contributes to the establishment of immunosuppressive microenvironment and facilitates tumor growth. Here, it have ingeniously designed multifunctional copper-piceatannol/HA nanopills (Cu-Pic/HA NPs) that effectively cause total intracellular polyamines depletion by inhibiting polyamines synthesis, depleting intracellular polyamines, and impairing polyamines uptake, resulting in enhanced pyroptosis and cuproptosis, thus activating a powerful immune response to achieve anti-tumor therapy. Mitochondrial dysfunction resulting from overall intracellular polyamines depletion not only leads to the surge of copper ions in mitochondria, thereby causing the aggregation of toxic proteins to induce cuproptosis, but also triggers the accumulation of reactive oxygen species (ROS) within mitochondria, which further upregulates the expression of zDHHC5 and zDHHC9 to promote the palmitoylation of gasdermin D (GSDMD) and GSDMD-N, ultimately inducing enhanced pyroptosis. Then the occurrence of enhanced pyroptosis and cuproptosis is conductive to remodel the immunosuppressive tumor microenvironment, thus activating anti-tumor immune responses and ultimately effectively inhibiting tumor growth and metastasis. This therapeutic strategy of enhanced pyroptosis and cuproptosis through comprehensive polyamines depletion provides a novel template for cancer immunotherapy |
|---|---|
| Beschreibung: | Date Completed 07.11.2024 Date Revised 07.11.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202409066 |