Co-delivery Nano System of MS-275 and V-9302 Induces Pyroptosis and Enhances Anti-Tumor Immunity Against Uveal Melanoma.
Adv Sci (Weinh)
; 11(31): e2404375, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38889339
ABSTRACT
In the treatment of uveal melanoma (UVM), histone deacetylase inhibitors (HDACi) have emerged as a promising epigenetic therapy. However, their clinical efficacy is hindered by the suboptimal pharmacokinetics and the strong self-rescue of tumor cells. To overcome these limitations, reactive oxygen species (ROS)-responsive nanoparticles (NPs) are designed that encapsulate HDACi MS-275 and the glutamine metabolism inhibitor V-9302. Upon reaching the tumor microenvironment, these NPs can disintegrate, thereby releasing MS-275 to increase the level of ROS and V-9302 to reduce the production of glutathione (GSH) related to self-rescue. These synergistic effects lead to a lethal ROS storm and induce cell pyroptosis. When combined with programmed cell death protein 1 monoclonal antibodies (α-PD-1), these NPs facilitate immune cell infiltration, improving anti-tumor immunity, converting "immune-cold" tumors into "immune-hot" tumors, and enhancing immune memory in mice. The findings present a nano-delivery strategy for the co-delivery of epigenetic therapeutics and metabolic inhibitors, which induces pyroptosis in tumors cells and improves the effectiveness of chemotherapy and immunotherapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Neoplasias Uveais
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Nanopartículas
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Piroptose
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Melanoma
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article