Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia

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 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. Graphical Abstract

Assembled polyphenol‐based systems as advanced therapeutics

“…The HA-EGCG was assembled with the antitumor drug sorafenib, leading to the formation of polymeric micelles. 113…”

“…117 Another noteworthy work by Bae et al involved the construction of a bone marrow-targetable EGCG-based sorafenib-loaded micellar nanocomplex (Sora-MNC) for synergistic therapy in acute myeloid leukemia. 113 In this study, EGCG was conjugated with HA to form HA-EGCG, and Sora-MNC was formed through the self-assembly of HA-EGCG and sorafenib. The inclusion of EGCG in Sora-MNC sensitized the therapeutic efficacy of sorafenib, while HA facilitated targeting via CD44 receptor recognition.…”

“…Bae et al conjugated hyaluronic acid (HA) with EGCG to form HA‐EGCG. The HA‐EGCG was assembled with the antitumor drug sorafenib, leading to the formation of polymeric micelles 113 …”

Toxicity and efficacy of green tea catechin derivative-based micellar nanocomplexes for anticancer protein delivery

“…This high-performance drug carrier has drawn attention as a promising approach to overcome the limitations of potential toxicity and insufficient drug delivery of conventional drug carriers. 27,28 Herceptin is a humanized monoclonal antibody against the human epidermal growth factor receptor (HER2/neu). 29 Herceptin induces regression of HER2/neu-overexpressing breast tumor tissue, and is not effective against tumors that do not overexpress HER2/neu.…”

“…This high-performance drug carrier has drawn attention as a promising approach to overcome the limitations of potential toxicity and insufficient drug delivery of conventional drug carriers. 27,28…”