2. Academic Validation
  3. Smart and Generalizable Cytarabine Derivative-Triggered Nanoparticles for Synergistic Therapy of Relapsed/Refractory Acute Myeloid Leukemia

Smart and Generalizable Cytarabine Derivative-Triggered Nanoparticles for Synergistic Therapy of Relapsed/Refractory Acute Myeloid Leukemia

  • ACS Appl Mater Interfaces. 2023 Jun 14;15(23):27624-27637. doi: 10.1021/acsami.3c03632.
Lejiao Jia 1,  Huatian Yang 2,  Dandan Zheng 2,  Jingjing Ye 3,  Qian Zhou 4,  Genjv Li 2,  Ying Zhou 3,  Xinyu Yang 3,  Jinting Liu 3,  Feng Ye 4,  Yuliang Song 4,  Daoxin Ma 3,  Chunyan Ji 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 2 Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 3 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 4 Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
PMID: 37249260 DOI: 10.1021/acsami.3c03632
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.

Keywords

BCL2; acute myeloid leukemia; cytarabine; redox-responsive; synergistic therapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-154971
    Cytarabine Derivative