Immunostimulatory nanoparticles delivering cytokines as a novel cancer nanoadjuvant to empower glioblastoma immunotherapy.
Cancer nanoadjuvant
Glioblastoma
IL-12
Immunostimulatory cytokines
Immunotherapy
Nanoparticles
Journal
Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061
Informations de publication
Date de publication:
31 Dec 2023
31 Dec 2023
Historique:
accepted:
18
12
2023
medline:
2
1
2024
pubmed:
2
1
2024
entrez:
31
12
2023
Statut:
aheadofprint
Résumé
Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood-brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype. However, systemic administration of IL-12 toxicity in clinical trials often leads to significant toxicity, posing a critical hurdle. To overcome this major drawback, we have formulated a novel nanoadjuvant composed of immunostimulatory nanoparticles (ISN) loaded with IL-12 to decrease IL-12 toxicity and enhance the immune response by macrophages and GBM cancer cells. Our in vitro results reveal that ISN substantially increase the production of pro-inflammatory cytokines in GBM cancer cells (e.g. 2.6 × increase in IL-8 expression compared to free IL-12) and macrophages (e.g. 2 × increase in TNF-α expression and 6 × increase in IL-6 expression compared to the free IL-12). These findings suggest a potential modulation of the tumor microenvironment. Additionally, our study demonstrates the effective intracellular delivery of IL-12 by ISN, triggering alterations in the levels of pro-inflammatory cytokines at both transcriptional and protein expression levels. These results highlight the promise of the nanoadjuvant as a prospective platform for resharing the GBM microenvironment and empowering immunotherapy.
Identifiants
pubmed: 38161192
doi: 10.1007/s13346-023-01509-2
pii: 10.1007/s13346-023-01509-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Center of Competence in Research Bio-Inspired Materials, University of Fribourg
ID : 205603
Informations de copyright
© 2023. The Author(s).
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