Abstract Background Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation.Results Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy.The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via FETs selective disruption of pro-survival mTOR signaling.In vivo biodistribution study demonstrated about 11-fold greater bone marrow accumulation of the nanocomplex compared to free sorafenib.In AML patient-derived xenograft (AML-PDX) mouse model, administration of the nanocomplex effectively eradicated bone marrow-residing leukemic blasts and improved survival rates without Connectors noticeable off-target toxicity.
Conclusion This study may provide insights into the rational design of nanomedicine platforms enabling bone marrow-targeted delivery of therapeutic agents for the treatment of AML and other bone marrow diseases.Graphical Abstract.