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

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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
Journal Title:
International Journal of Molecular Sciences
Publication Date:
26 December 2022
Citation:
Bae, K. H., Lai, F., Oruc, B., Osato, M., Chen, Q., & Kurisawa, M. (2022). Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia. International Journal of Molecular Sciences, 24(1), 381. https://doi.org/10.3390/ijms24010381
Abstract:
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research is supported by core funding from: BMRC
Grant Reference no. : NIL
Description:
ISSN:
1422-0067
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