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Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy.
- Source :
-
Biomaterials [Biomaterials] 2024 Dec; Vol. 311, pp. 122645. Date of Electronic Publication: 2024 May 28. - Publication Year :
- 2024
-
Abstract
- Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Mice
Tissue Scaffolds chemistry
Cell Line, Tumor
Mice, Inbred C57BL
Neoplasms therapy
Neoplasms drug therapy
Neoplasms immunology
Humans
Female
Mice, Inbred BALB C
Membrane Proteins agonists
Membrane Proteins metabolism
Immunotherapy methods
Proto-Oncogene Proteins c-akt metabolism
Printing, Three-Dimensional
Heterocyclic Compounds, 3-Ring pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 311
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 38850717
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2024.122645