Abstract
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.
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