A Selective Nano Cell Cycle Checkpoint Inhibitor Overcomes Leukemia Chemoresistance.
Small
; 19(25): e2300736, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-37029565
ABSTRACT
Cell cycle checkpoint activation promotes DNA damage repair, which is highly associated with the chemoresistance of various cancers including acute myeloid leukemia (AML). Selective cell cycle checkpoint inhibitors are strongly demanded to overcome chemoresistance, but remain unexplored. A selective nano cell cycle checkpoint inhibitor (NCCI citric acid capped ultra-small iron oxide nanoparticles) that can catalytically inhibit the cell cycle checkpoint of AML to boost the chemotherapeutic efficacy of genotoxic agents is now reported. NCCI can selectively accumulate in AML cells and convert H2 O2 to ⢠OH to cleave heat shock protein 90, leading to the degradation of ataxia telangiectasia and Rad3-related proteinand checkpoint kinase 1, and the subsequent dysfunction of the G2/M checkpoint. Consequently, NCCI revitalizes the anti-AML efficacy of cytarabine that is previously ineffective both in vitro and in vivo. This study offers new insights into designing selective cell cycle checkpoint inhibitors for biomedical applications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Resistencia a Antineoplásicos
/
Puntos de Control del Ciclo Celular
/
Nanopartículas Magnéticas de Óxido de Hierro
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Small
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China