Citation: Liangyu Zhang, Lei Lei, Zhuangzhuang Zhao, Guizhi Yang, Kaitao Wang, Liying Wang, Ningxin Zhang, Yanjia Ai, Xinqing Ma, Guannan Liu, Meng Zhao, Jun Wu, Dongjun Lin, Chun Chen. Enhanced venetoclax delivery using l-phenylalanine nanocarriers in acute myeloid leukemia treatment[J]. Chinese Chemical Letters, ;2025, 36(6): 110316. doi: 10.1016/j.cclet.2024.110316 shu

Enhanced venetoclax delivery using l-phenylalanine nanocarriers in acute myeloid leukemia treatment

Liangyu Zhang ^{a, b, 1} ,
Lei Lei ^{c, 1} ,
Zhuangzhuang Zhao ^{d, 1} ,
Guizhi Yang ^b ,
Kaitao Wang ^{a, b} ,
Liying Wang ^a ,
Ningxin Zhang ^e ,
Yanjia Ai ^e ,
Xinqing Ma ^b ,
Guannan Liu ^b ,
Meng Zhao ^{a, b, f, *,} ,
Jun Wu ^{a, g, h, *,} ,
Dongjun Lin ^{a, *,} ,
Chun Chen ^{i, *,}

a.
Department of Hematology, The Seventh Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Shenzhen 518107, China
b.
Key Laboratory of Stem Cells and Tissue Engineering (Ministry of Education), Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
c.
Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Shenzhen 518107, China
d.
Changzhi Medical College, Changzhi 046000, China
e.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
f.
Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
g.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China
h.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China
i.
Department of Pediatrics, The Seventh Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Shenzhen 518107, China

zhaom38@mail.sysu.edu.cn

junwuhkust@ust.hk

lindongjun0168@163.com

chenchun@mail.sysu.edu.cn

Received Date: 11 June 2024
Revised Date: 3 August 2024
Accepted Date: 5 August 2024
Available Online: 5 August 2024

Figures(4)

Venetoclax (Vene), a BCL-2 inhibitor, is widely used as a chemotherapeutic drug in acute myeloid leukemia (AML). However, its treatment specificity for leukemia cells is limited, often leading to side effects and treatment resistance. In this study, we utilized l-phenylalanine as an efficient nanocarrier to enhance the delivery of Vene, forming the complex Vene@8P6. This complex was then applied to AML mouse models and human AML cell lines. The in vitro analysis showed that THP-1 and HL60 cells rapidly absorbed the Vene@8P6 nanoparticles. This absorption resulted in severe DNA damage, increased reactive oxygen species (ROS) production, elevated apoptosis rates, and decreased cell proliferation compared to the administration of Vene alone. In vivo studies demonstrated that Vene@8P6 more efficiently targeted leukemia cells than normal hematopoietic cells within the bone marrow and other major organs in AML mice, as evidenced by bioluminescence imaging and flow cytometry analysis. Furthermore, Vene@8P6 treatment resulted in reduced drug side effects and improved therapeutic efficacy in AML mice. Overall, Vene@8P6 represents a novel and efficient therapeutic agent for AML, offering enhanced leukemia target specificity, reduced side effects, and improved treatment outcomes.
- Acute myeloid leukemia,
- Venetoclax,
- l-Phenylalanine,
- Chemoresistance,
- Nanoparticles
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