Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma

Jinran Li,1 Yuxi Jia,1 Peng Zhang,2 Huailin Yang,2 Xianling Cong,1 Lin An,3 Chunsheng Xiao2,4 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chem...

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Autores principales:	Li J, Jia Y, Zhang P, Yang H, Cong X, An L, Xiao C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	celastrol self-assembly self-stabilization nanomedicine melanoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/30f802ed81004b73aa22c13b7723cf0e
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spelling	oai:doaj.org-article:30f802ed81004b73aa22c13b7723cf0e2021-12-02T05:44:58ZCelastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma1178-2013https://doaj.org/article/30f802ed81004b73aa22c13b7723cf0e2020-02-01T00:00:00Zhttps://www.dovepress.com/celastrol-self-stabilized-nanoparticles-for-effective-treatment-of-mel-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jinran Li,1 Yuxi Jia,1 Peng Zhang,2 Huailin Yang,2 Xianling Cong,1 Lin An,3 Chunsheng Xiao2,4 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China; 3Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 4Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, People’s Republic of ChinaCorrespondence: Xianling Cong; Lin An Tel +86-431-89876626; +86-431-84995523Email congxl@jlu.edu.cn; anlin.changchun@163.comBackground: 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.Keywords: celastrol, self-assembly, self-stabilization, nanomedicine, melanomaLi JJia YZhang PYang HCong XAn LXiao CDove Medical Pressarticlecelastrolself-assemblyself-stabilizationnanomedicinemelanomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1205-1214 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	celastrol self-assembly self-stabilization nanomedicine melanoma Medicine (General) R5-920
spellingShingle	celastrol self-assembly self-stabilization nanomedicine melanoma Medicine (General) R5-920 Li J Jia Y Zhang P Yang H Cong X An L Xiao C Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
description	Jinran Li,1 Yuxi Jia,1 Peng Zhang,2 Huailin Yang,2 Xianling Cong,1 Lin An,3 Chunsheng Xiao2,4 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China; 3Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 4Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, People’s Republic of ChinaCorrespondence: Xianling Cong; Lin An Tel +86-431-89876626; +86-431-84995523Email congxl@jlu.edu.cn; anlin.changchun@163.comBackground: 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.Keywords: celastrol, self-assembly, self-stabilization, nanomedicine, melanoma
format	article
author	Li J Jia Y Zhang P Yang H Cong X An L Xiao C
author_facet	Li J Jia Y Zhang P Yang H Cong X An L Xiao C
author_sort	Li J
title	Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma
title_short	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_sort	celastrol self-stabilized nanoparticles for effective treatment of melanoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/30f802ed81004b73aa22c13b7723cf0e
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Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma

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