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Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma

BACKGROUND: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. PURPOSE: We proposed a facile...

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Autores principales: Li, Jinran, Jia, Yuxi, Zhang, Peng, Yang, Huailin, Cong, Xianling, An, Lin, Xiao, Chunsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037082/
https://www.ncbi.nlm.nih.gov/pubmed/32110017
http://dx.doi.org/10.2147/IJN.S232603
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author Li, Jinran
Jia, Yuxi
Zhang, Peng
Yang, Huailin
Cong, Xianling
An, Lin
Xiao, Chunsheng
author_facet Li, Jinran
Jia, Yuxi
Zhang, Peng
Yang, Huailin
Cong, Xianling
An, Lin
Xiao, Chunsheng
author_sort Li, Jinran
collection PubMed
description BACKGROUND: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. PURPOSE: We proposed a facile “in situ drug conjugation-induced self-assembly” strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. METHODS: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. RESULTS: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. CONCLUSION: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.
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spelling pubmed-70370822020-02-27 Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma Li, Jinran Jia, Yuxi Zhang, Peng Yang, Huailin Cong, Xianling An, Lin Xiao, Chunsheng Int J Nanomedicine Original Research BACKGROUND: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. PURPOSE: We proposed a facile “in situ drug conjugation-induced self-assembly” strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. METHODS: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. RESULTS: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. CONCLUSION: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy. Dove 2020-02-19 /pmc/articles/PMC7037082/ /pubmed/32110017 http://dx.doi.org/10.2147/IJN.S232603 Text en © 2020 Li et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Li, Jinran
Jia, Yuxi
Zhang, Peng
Yang, Huailin
Cong, Xianling
An, Lin
Xiao, Chunsheng
Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_full Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_fullStr Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_full_unstemmed Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_short Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_sort celastrol self-stabilized nanoparticles for effective treatment of melanoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037082/
https://www.ncbi.nlm.nih.gov/pubmed/32110017
http://dx.doi.org/10.2147/IJN.S232603
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