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靶向骨髓的基于绿茶儿茶素的胶束纳米复合物用于协同治疗急性髓系白血病。

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

机构信息

Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.

Institute of Molecular and Cell Biology, 61 Biopolis Drive, The Proteos, Singapore, 138673, Singapore.

出版信息

J Nanobiotechnology. 2022 Nov 16;20(1):481. doi: 10.1186/s12951-022-01683-4.

DOI:10.1186/s12951-022-01683-4
PMID:36384529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9670631/
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.

摘要

背景

由于现有抗白血病药物进入骨髓龛支持白血病细胞增殖的能力有限，因此在治疗急性髓系白血病 (AML) 方面的疗效有限。

结果

本文报道了一种基于绿茶儿茶素的骨髓靶向胶束纳米复合物，用于协同治疗 AML。研究发现，该纳米复合物通过选择性破坏生存 mTOR 信号，协同增强索拉非尼的抗白血病活性。体内生物分布研究表明，与游离索拉非尼相比，纳米复合物在骨髓中的积累增加了约 11 倍。在 AML 患者来源异种移植 (AML-PDX) 小鼠模型中，纳米复合物的给药有效地消除了骨髓中残留的白血病母细胞，并提高了存活率，而没有明显的脱靶毒性。

结论

这项研究可能为合理设计纳米医学平台提供思路，使治疗 AML 和其他骨髓疾病的治疗药物能够靶向骨髓递药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/c8115ee9db06/12951_2022_1683_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/ab3e95e88a48/12951_2022_1683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/12df0cb0e4ba/12951_2022_1683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/07199cbace9c/12951_2022_1683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/a6fd2a320d1c/12951_2022_1683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/2a2c8bda2958/12951_2022_1683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/c8115ee9db06/12951_2022_1683_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/ab3e95e88a48/12951_2022_1683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/12df0cb0e4ba/12951_2022_1683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/07199cbace9c/12951_2022_1683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/a6fd2a320d1c/12951_2022_1683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/2a2c8bda2958/12951_2022_1683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d183/9670631/c8115ee9db06/12951_2022_1683_Fig6_HTML.jpg

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