Programmed Targeting Pyruvate Metabolism Therapy Amplified Single-Atom Nanozyme-Activated Pyroptosis for Immunotherapy.
Adv Mater
; 36(24): e2312124, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38314930
ABSTRACT
Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single-atom nanozyme pyroptosis initiator UK5099 and pyruvate oxidase (POx)-co-loaded Cu-NS single-atom nanozyme (Cu-NS@UK@POx), that not only trigger pyroptosis through cascade biocatalysis to boost the immunogenicity of tumor cells, but also remodel the immunosuppressive TME by targeting pyruvate metabolism. By replacing N with weakly electronegative S, the original spatial symmetry of the Cu-N4 electron distribution is changed and the enzyme-catalyzed process is effectively regulated. Compared to spatially symmetric Cu-N4 single-atom nanozymes (Cu-N4 SA), the S-doped spatially asymmetric single-atom nanozymes (Cu-NS SA) exhibit stronger oxidase activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) oxidase (NOx), L-cysteine oxidase (LCO), and glutathione oxidase (GSHOx), which can cause enough reactive oxygen species (ROS) storms to trigger pyroptosis. Moreover, the synergistic effect of Cu-NS SA, UK5099, and POx can target pyruvate metabolism, which not only improves the immune TME but also increases the degree of pyroptosis. This study provides a two-pronged treatment strategy that can significantly activate antitumor immunotherapy effects via ROS storms, NADH/glutathione/L-cysteine consumption, pyruvate oxidation, and lactic acid (LA)/ATP depletion, triggering pyroptosis and regulating metabolism. This work provides a broad vision for expanding antitumor immunotherapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Pirúvico
/
Piroptose
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Imunoterapia
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article