STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 03 2023
23 03 2023
Historique:
received:
24
06
2022
accepted:
08
03
2023
entrez:
24
3
2023
pubmed:
25
3
2023
medline:
28
3
2023
Statut:
epublish
Résumé
As a key component of the standard of care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation of CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. We show that the engager B-LNPs block CD47 and PD-L1 and promote TAMC phagocytic activity. To enhance subsequent T cell recruitment and antitumor responses after tumor engulfment, the B-LNP was encapsulated with diABZI, a non-nucleotidyl agonist for stimulator of interferon genes. In vivo treatment with diABZI-loaded B-LNPs induced a transcriptomic and metabolic switch in TAMCs, turning these immunosuppressive cells into antitumor effectors, which induced T cell infiltration and activation in brain tumors. In preclinical murine models, B-LNP/diABZI administration synergized with radiotherapy to promote brain tumor regression and induce immunological memory against glioma. In summary, our study describes a nanotechnology-based approach that hijacks irradiation-triggered immune checkpoint molecules to boost potent and long-lasting antitumor immunity against glioblastoma.
Identifiants
pubmed: 36959214
doi: 10.1038/s41467-023-37328-9
pii: 10.1038/s41467-023-37328-9
pmc: PMC10036562
doi:
Substances chimiques
B7-H1 Antigen
0
CD47 Antigen
0
CD47 protein, human
0
Interferons
9008-11-1
STING1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1610Subventions
Organisme : NCI NIH HHS
ID : R37 CA266487
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221747
Pays : United States
Informations de copyright
© 2023. The Author(s).
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