Hypoxia-activated glutamine antagonist prodrug combined with combretastatin A4 nanoparticles for tumor-selective metabolic blockade.
J Control Release
; 365: 480-490, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38040341
ABSTRACT
6-Diazo-5-oxo-L-norleucine (DON) is a potent glutamine antagonist with toxic side effects; in order to reduce these effects, multiple prodrugs have been designed. However, there are currently no reports of a DON prodrug with a defined mechanism to achieve high tumor selectivity. To improve the selective toxicity of DON to tumor cells while reducing systemic toxicity, a hypoxia-activated prodrug, termed HDON, was designed. HDON achieved remarkable tumor suppression of 76.4 ± 5.2% without leading to weight loss in an H22 murine liver cancer model with high hypoxia. Moreover, to augment the therapeutic efficacy of HDON, combretastatin A4 nanoparticles were used to aggravate tumor hypoxia of MC38 murine colon cancer and 4T1 murine breast cancer, activate HDON to DON, and stimulate a robust anti-tumor immune response while selectively killing in tumor cells in vivo, achieving significantly elevated tumor suppression rates of 98.3 ± 3.4% and 98.1 ± 3.1%, with cure rates of 80.0% and 20.0%, respectively.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Neoplasias da Mama
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Pró-Fármacos
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Nanopartículas
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China