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

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...

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Autores principales: Bae, Ki Hyun, Lai, Fritz, Mong, Jamie, Niibori-Nambu, Akiko, Chan, Kiat Hwa, Her, Zhisheng, Osato, Motomi, Tan, Min-Han, Chen, Qingfeng, Kurisawa, Motoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670631/
https://www.ncbi.nlm.nih.gov/pubmed/36384529
http://dx.doi.org/10.1186/s12951-022-01683-4
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author Bae, Ki Hyun
Lai, Fritz
Mong, Jamie
Niibori-Nambu, Akiko
Chan, Kiat Hwa
Her, Zhisheng
Osato, Motomi
Tan, Min-Han
Chen, Qingfeng
Kurisawa, Motoichi
author_facet Bae, Ki Hyun
Lai, Fritz
Mong, Jamie
Niibori-Nambu, Akiko
Chan, Kiat Hwa
Her, Zhisheng
Osato, Motomi
Tan, Min-Han
Chen, Qingfeng
Kurisawa, Motoichi
author_sort Bae, Ki Hyun
collection PubMed
description 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01683-4.
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spelling pubmed-96706312022-11-18 Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia Bae, Ki Hyun Lai, Fritz Mong, Jamie Niibori-Nambu, Akiko Chan, Kiat Hwa Her, Zhisheng Osato, Motomi Tan, Min-Han Chen, Qingfeng Kurisawa, Motoichi J Nanobiotechnology Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01683-4. BioMed Central 2022-11-16 /pmc/articles/PMC9670631/ /pubmed/36384529 http://dx.doi.org/10.1186/s12951-022-01683-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bae, Ki Hyun
Lai, Fritz
Mong, Jamie
Niibori-Nambu, Akiko
Chan, Kiat Hwa
Her, Zhisheng
Osato, Motomi
Tan, Min-Han
Chen, Qingfeng
Kurisawa, Motoichi
Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title_full Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title_fullStr Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title_full_unstemmed Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title_short Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
title_sort bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic therapy of acute myeloid leukemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670631/
https://www.ncbi.nlm.nih.gov/pubmed/36384529
http://dx.doi.org/10.1186/s12951-022-01683-4
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