Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes

Yufei Feng,1 Guozhao Qin,1 Shuyuan Chang,1 Zhongxu Jing,2 Yanyan Zhang,1 Yanhong Wang1 1Key Laboratory of Chinese Materia Medica in Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Heilongjiang Provincial Administration...

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Autores principales:	Feng Y, Qin G, Chang S, Jing Z, Zhang Y, Wang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mitochondria-targeted liposome charge reversal antitumor hyperoside Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/23321fa66b7442f09baacd7f1500c35a
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spelling	oai:doaj.org-article:23321fa66b7442f09baacd7f1500c35a2021-12-02T17:00:09ZAntitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes1178-2013https://doaj.org/article/23321fa66b7442f09baacd7f1500c35a2021-04-01T00:00:00Zhttps://www.dovepress.com/antitumor-effect-of-hyperoside-loaded-in-charge-reversed-and-mitochond-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Yufei Feng,1 Guozhao Qin,1 Shuyuan Chang,1 Zhongxu Jing,2 Yanyan Zhang,1 Yanhong Wang1 1Key Laboratory of Chinese Materia Medica in Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Heilongjiang Provincial Administration of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Yanhong Wang Tel +86451-87266893Email 799378826@qq.comIntroduction: Hyperoside (HYP), a flavonol glycoside compound, has been shown to significantly inhibit the proliferation of malignant tumors. Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy.Objective: We report a novel dual-functional liposome system possessing both extracellular charge reversal and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of cancer cells.Methods: L-lysine was used as a linker to connect 2,3-dimethylmaleic anhydride (DMA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a new compound, DSPE-Lys-DMA (DLD). Then, DLD was mixed with other commercially available lipids to form charge reversed and mitochondria-targeted liposomes (DLD-Lip). The size, morphology, zeta potential, serum stability, and protein adsorption of the HYP loaded DLD-Lip (HYP/DLD-Lip) were measured. The release profile, cellular uptake, in vitro and in vivo toxicity, and anticancer activity of HYP/DLD-Lip were investigated.Results: The results showed that the mean diameter of the liposomes was less than 200 nm. The zeta potential of the liposomes was negative at pH 7.4. However, the zeta potential was positive at weak acidic pH values with the cleavage of the DMA amide. The charge reversion of HYP/DLD-Lip facilitated the cellular internalization and mitochondrial accumulation for enhanced antitumor effect. The strongest tumor growth inhibition (TGI 88.79%) without systemic toxicity was observed in DLD/HYP-Lips-treated CBRH-7919 tumor xenograft BALB/C mice.Conclusion: The charge reversed and mitochondria-targeted liposomes represented a promising anticancer drug delivery system for enhanced anticancer therapeutic efficacy.Keywords: mitochondria-targeted, liposome, charge reversal, antitumor, hyperosideFeng YQin GChang SJing ZZhang YWang YDove Medical Pressarticlemitochondria-targetedliposomecharge reversalantitumorhyperosideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 3073-3089 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria-targeted liposome charge reversal antitumor hyperoside Medicine (General) R5-920
spellingShingle	mitochondria-targeted liposome charge reversal antitumor hyperoside Medicine (General) R5-920 Feng Y Qin G Chang S Jing Z Zhang Y Wang Y Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
description	Yufei Feng,1 Guozhao Qin,1 Shuyuan Chang,1 Zhongxu Jing,2 Yanyan Zhang,1 Yanhong Wang1 1Key Laboratory of Chinese Materia Medica in Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Heilongjiang Provincial Administration of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Yanhong Wang Tel +86451-87266893Email 799378826@qq.comIntroduction: Hyperoside (HYP), a flavonol glycoside compound, has been shown to significantly inhibit the proliferation of malignant tumors. Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy.Objective: We report a novel dual-functional liposome system possessing both extracellular charge reversal and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of cancer cells.Methods: L-lysine was used as a linker to connect 2,3-dimethylmaleic anhydride (DMA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a new compound, DSPE-Lys-DMA (DLD). Then, DLD was mixed with other commercially available lipids to form charge reversed and mitochondria-targeted liposomes (DLD-Lip). The size, morphology, zeta potential, serum stability, and protein adsorption of the HYP loaded DLD-Lip (HYP/DLD-Lip) were measured. The release profile, cellular uptake, in vitro and in vivo toxicity, and anticancer activity of HYP/DLD-Lip were investigated.Results: The results showed that the mean diameter of the liposomes was less than 200 nm. The zeta potential of the liposomes was negative at pH 7.4. However, the zeta potential was positive at weak acidic pH values with the cleavage of the DMA amide. The charge reversion of HYP/DLD-Lip facilitated the cellular internalization and mitochondrial accumulation for enhanced antitumor effect. The strongest tumor growth inhibition (TGI 88.79%) without systemic toxicity was observed in DLD/HYP-Lips-treated CBRH-7919 tumor xenograft BALB/C mice.Conclusion: The charge reversed and mitochondria-targeted liposomes represented a promising anticancer drug delivery system for enhanced anticancer therapeutic efficacy.Keywords: mitochondria-targeted, liposome, charge reversal, antitumor, hyperoside
format	article
author	Feng Y Qin G Chang S Jing Z Zhang Y Wang Y
author_facet	Feng Y Qin G Chang S Jing Z Zhang Y Wang Y
author_sort	Feng Y
title	Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
title_short	Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
title_full	Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
title_fullStr	Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
title_full_unstemmed	Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes
title_sort	antitumor effect of hyperoside loaded in charge reversed and mitochondria-targeted liposomes
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/23321fa66b7442f09baacd7f1500c35a
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Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes

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