Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy.
Biomaterials
; 311: 122645, 2024 Dec.
Article
in En
| MEDLINE
| ID: mdl-38850717
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-akt
/
Printing, Three-Dimensional
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Heterocyclic Compounds, 3-Ring
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Immunotherapy
/
Membrane Proteins
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Biomaterials
Year:
2024
Document type:
Article
Affiliation country:
China