Novel Photo-STING Agonists Delivered by Erythrocyte Efferocytosis-Mimicking Pattern to Repolarize Tumor-Associated Macrophages for Boosting Anticancer Immunotherapy
© 2024 Wiley‐VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - (2024) vom: 08. Okt., Seite e2410937 |
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| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article cGAS‐STING signaling pathway immunotherapy manganese nanomedicine reactive oxygen species |
| Zusammenfassung: | © 2024 Wiley‐VCH GmbH. Immunotherapy has emerged as a highly effective therapeutic strategy for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway activation facilitates tumor-associated macrophage (TAM) polarization toward M1 phenotype, and Mn2+ are effective agents for this pathway activation. However, the high in vivo degradation rate and toxicity of Mn2+ hamper clinical application of immunotherapy. Here, this work has newly synthesized and screened manganese porphyrins for Mn2+ transport, referred to as photo-STING agonists (PSAs), and further encapsulate them into core-shell nanoparticles named RmPP-GA with dual specificity for tumor tissue and TAMs. Not only do PSAs achieve higher Mn2+ delivery efficiency compared to Mn2+, but they also generate reactive oxygen species under light exposure, promoting mitochondrial DNA release for cGAS-STING pathway activation. In Rm@PP-GA, globin and red blood cell membranes (Rm) are used for erythrocyte efferocytosis-mimicking delivery. Rm can effectively prolong the in vivo circulation period while globin enables PSAs to be taken up by TAMs via CD163 receptors. After Rm rupture mediated by perfluorohexane in nanoparticles under ultrasonication, drugs are specifically released for TAM repolarization. Further, dendritic cells mature, as well as T lymphocyte infiltrate, both of which favor tumor eradication. Therefore, cancer immunotherapy is optimized by novel PSAs delivered by erythrocyte efferocytosis-mimicking delivery pattern |
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| Beschreibung: | Date Revised 09.10.2024 published: Print-Electronic Citation Status Publisher |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202410937 |