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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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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. |
format | Online Article Text |
id | pubmed-7037082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
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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