Smart and Generalizable Cytarabine Derivative-Triggered Nanoparticles for Synergistic Therapy of Relapsed/Refractory Acute Myeloid Leukemia.
ACS Appl Mater Interfaces
; 15(23): 27624-27637, 2023 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-37249260
ABSTRACT
Acute myeloid leukemia (AML) is rapidly progressed hematologic malignancy with relapsed and refractory characteristics. Cytarabine combined with the BCL2 inhibitor venetoclax showed impressive response rates in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML), while it requires complicated administration regimens and brings added toxicity. In this work, we synthesized a mercaptopropionic acid-substituted derivative of Ara-C (Ara-SH) and used it as the trigger to fabricate a smart cytarabine and venetoclax-coloaded nanoparticle (AV-NP) through self-assembly. The AV-NP characterized with redox-responsive drug release, rapid uptake by leukemia cells, and long retention in circulation had the potential to accumulate in leukemia-enriched sites. It generated a remarkable synergistic effect with higher antileukemia activity in vitro and better safety in the hematologic system compared with free drugs and significantly improved the therapeutic effect on orthotopic AML mice in vivo. These similar results were also confirmed in primary cells from R/R-AML patients. Besides, the AV-NP has the superiority of facile fabrication and generalizability, rendering it easy for clinical translation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Citarabina
Límite:
Animals
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China