A DNA-Modularized STING Agonist with Macrophage-Selectivity and Programmability for Enhanced Anti-Tumor Immunotherapy.
Adv Sci (Weinh)
; 11(32): e2400149, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38898748
ABSTRACT
The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS-STING pathway activation, macrophage-selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer- or lipid-based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage-selective uptake and programmable activation of the cGAS-STING pathway through precise self-assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage-selective uptake, endosomal escape, and cytosolic release of the cGAS-recognizing DNA segment, leading to robust activation of the cGAS-STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS-STING activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
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Imunoterapia
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Macrófagos
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Proteínas de Membrana
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Nucleotidiltransferases
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article