Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784865427538575360 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9820275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT baekihyun selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia AT laifritz selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia AT orucbetul selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia AT osatomotomi selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia AT chenqingfeng selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia AT kurisawamotoichi selfassembleddaunorubicinepigallocatechingallatenanocomplexforsynergisticreversalofchemoresistanceinleukemia |