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Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia

Chemoresistance is one of the major challenges for the treatment of acute myeloid leukemia. Epigallocatechin gallate (EGCG), a bioactive polyphenol from green tea, has attracted immense interest as a potential chemosensitizer, but its application is limited due to the need for effective formulations...

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Autores principales: Bae, Ki Hyun, Lai, Fritz, Oruc, Betul, Osato, Motomi, Chen, Qingfeng, Kurisawa, Motoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820275/
https://www.ncbi.nlm.nih.gov/pubmed/36613821
http://dx.doi.org/10.3390/ijms24010381
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author Bae, Ki Hyun
Lai, Fritz
Oruc, Betul
Osato, Motomi
Chen, Qingfeng
Kurisawa, Motoichi
author_facet Bae, Ki Hyun
Lai, Fritz
Oruc, Betul
Osato, Motomi
Chen, Qingfeng
Kurisawa, Motoichi
author_sort Bae, Ki Hyun
collection PubMed
description Chemoresistance is one of the major challenges for the treatment of acute myeloid leukemia. Epigallocatechin gallate (EGCG), a bioactive polyphenol from green tea, has attracted immense interest as a potential chemosensitizer, but its application is limited due to the need for effective formulations capable of co-delivering EGCG and anti-leukemic drugs. Herein, we describe the formation and characterization of a micellar nanocomplex self-assembled from EGCG and daunorubicin, an anthracycline drug for the first-line treatment of acute myeloid leukemia. This nanocomplex was highly stable at pH 7.4 but stimulated to release the incorporated daunorubicin at pH 5.5, mimicking an acidic endosomal environment. More importantly, the nanocomplex exhibited superior cytotoxic efficacy against multidrug-resistant human leukemia cells over free daunorubicin by achieving a strong synergism, as supported by median-effect plot analysis. The observed chemosensitizing effect was in association with enhanced nucleus accumulation of daunorubicin, elevation of intracellular reactive oxygen species and caspase-mediated apoptosis induction. Our study presents a promising strategy for circumventing chemoresistance for more effective leukemia therapy.
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spelling pubmed-98202752023-01-07 Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia Bae, Ki Hyun Lai, Fritz Oruc, Betul Osato, Motomi Chen, Qingfeng Kurisawa, Motoichi Int J Mol Sci Article Chemoresistance is one of the major challenges for the treatment of acute myeloid leukemia. Epigallocatechin gallate (EGCG), a bioactive polyphenol from green tea, has attracted immense interest as a potential chemosensitizer, but its application is limited due to the need for effective formulations capable of co-delivering EGCG and anti-leukemic drugs. Herein, we describe the formation and characterization of a micellar nanocomplex self-assembled from EGCG and daunorubicin, an anthracycline drug for the first-line treatment of acute myeloid leukemia. This nanocomplex was highly stable at pH 7.4 but stimulated to release the incorporated daunorubicin at pH 5.5, mimicking an acidic endosomal environment. More importantly, the nanocomplex exhibited superior cytotoxic efficacy against multidrug-resistant human leukemia cells over free daunorubicin by achieving a strong synergism, as supported by median-effect plot analysis. The observed chemosensitizing effect was in association with enhanced nucleus accumulation of daunorubicin, elevation of intracellular reactive oxygen species and caspase-mediated apoptosis induction. Our study presents a promising strategy for circumventing chemoresistance for more effective leukemia therapy. MDPI 2022-12-26 /pmc/articles/PMC9820275/ /pubmed/36613821 http://dx.doi.org/10.3390/ijms24010381 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bae, Ki Hyun
Lai, Fritz
Oruc, Betul
Osato, Motomi
Chen, Qingfeng
Kurisawa, Motoichi
Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title_full Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title_fullStr Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title_full_unstemmed Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title_short Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
title_sort self-assembled daunorubicin/epigallocatechin gallate nanocomplex for synergistic reversal of chemoresistance in leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820275/
https://www.ncbi.nlm.nih.gov/pubmed/36613821
http://dx.doi.org/10.3390/ijms24010381
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