Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-022-01683-4
Keywords
Bone marrow; Targeting; Sorafenib; Micellar nanocomplex; Leukemia
Funding
- Institute of Bioengineering and Bioimaging, and the Institute of Molecular and Cell Biology (Biomedical Research Council, Agency for Science, Technology and Research (A*STAR)), Singapore
- National Research Foundation Singapore Fellowship [NRF-NRFF2017-03]
- Industry Alignment Fund -Industry Collaboration Projects (IAF-ICP) Grant [ICP-2000120]
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This study presents a bone marrow-targetable green tea catechin-based micellar nanocomplex that synergistically enhances the anti-leukemic potency of sorafenib. It demonstrates effective eradication of leukemic blasts in bone marrow and improved survival rates in an AML-PDX mouse model.
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 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 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.
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