Bae, K. H., Lai, F., Mong, J., Niibori-Nambu, A., Chan, K. H., Her, Z., Osato, M., Tan, M.-H., Chen, Q., & Kurisawa, M. (2022). Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia. Journal of Nanobiotechnology, 20(1). https://doi.org/10.1186/s12951-022-01683-4
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.
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.
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.
Attribution 4.0 International (CC BY 4.0)
This research / project is supported by the National Research Foundation - Singapore Fellowship
Grant Reference no. : NRF-NRFF2017-03
This research / project is supported by the A*STAR - Industry Alignment Fund - Industry Collaboration Projects (IAF-ICP) Grant
Grant Reference no. : ICP-2000120
This research is supported by core funding from: A*STAR BMRC
Grant Reference no. : NA