Immunostimulatory silica nanoparticle boosts innate immunity in brain tumors
| Autor: | Gil Covarrubias, Taylor J. Moon, Shruthi Ravichandran, Efstathios Karathanasis, Prabhani U. Atukorale, Peter Bielecki, Michelle L. Wiese, Morgan E Lorkowski, Yahan Zhang, Wyatt M. Becicka |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class medicine.medical_treatment T cell Antigen-Presenting Cells Antineoplastic Agents CD8-Positive T-Lymphocytes Article Mice 03 medical and health sciences 0302 clinical medicine Immune system Interferon Tumor Microenvironment Animals Immunologic Factors Medicine General Materials Science Cyclic GMP Tumor microenvironment Innate immune system Brain Neoplasms business.industry Macrophages Dendritic Cells Silicon Dioxide Immunity Innate Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Interferon Type I Cancer research Nanoparticles Female Immunotherapy sense organs Glioblastoma business Porosity CD8 medicine.drug |
| Zdroj: | Nanoscale Horiz |
| ISSN: | 2055-6764 2055-6756 |
| DOI: | 10.1039/d0nh00446d |
| Popis: | The high mortality associated with glioblastoma multiforme (GBM) is attributed to its invasive nature, hypoxic core, resistant cell subpopulations and a highly immunosuppressive tumor microenvironment (TME). To support adaptive immune function and establish a more robust antitumor immune response, we boosted the local innate immune compartment of GBM using an immunostimulatory mesoporous silica nanoparticle, termed immuno-MSN. The immuno-MSN was specifically designed for systemic and proficient delivery of a potent innate immune agonist to dysfunctional antigen-presenting cells (APCs) in the brain TME. The cargo of the immuno-MSN was cyclic diguanylate monophosphate (cdGMP), a Stimulator of Interferon Gene (STING) agonist. Studies showed the immuno-MSN promoted the uptake of STING agonist by APCs in vitro and the subsequent release of the pro-inflammatory cytokine interferon β, 6-fold greater than free agonist. In an orthotopic GBM mouse model, systemically administered immuno-MSN particles were taken up by APCs in the near-perivascular regions of the brain tumor with striking efficiency. The immuno-MSNs facilitated the recruitment of dendritic cells and macrophages to the TME while sparing healthy brain tissue and peripheral organs, resulting in elevated circulating CD8(+) T cell activity (2.5-fold) and delayed GBM tumor growth. We show that an engineered immunostimulatory nanoparticle can support pro-inflammatory innate immune function in GBM and subsequently augment current immunotherapeutic interventions and improve their therapeutic outcome. |
| Databáze: | OpenAIRE |
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