Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells

Yueling Yuan,1,* Tiange Cai,2,* Richard Callaghan,3,* Qianwen Li,4 Yinghong Huang,4 Bingyue Wang,1 Qingqing Huang,1 Manling Du,1 Qianqian Ma,1 Peter Chiba,5 Yu Cai1,6 1College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China; 2College of Life Science, Liaoning University, Shenyang,...

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Autores principales:	Yuan Y, Cai T, Callaghan R, Li Q, Huang Y, Wang B, Huang Q, Du M, Ma Q, Chiba P, Cai Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Lipid-polymer hybrid nanoparticles psoralen drug delivery HepG2/ADR cells apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/54881fbd6ddb4cd285b70a4c68b2e85a
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spelling	oai:doaj.org-article:54881fbd6ddb4cd285b70a4c68b2e85a2021-12-02T08:52:56ZPsoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells1178-2013https://doaj.org/article/54881fbd6ddb4cd285b70a4c68b2e85a2019-03-01T00:00:00Zhttps://www.dovepress.com/psoralen-loaded-lipid-polymer-hybrid-nanoparticles-enhance-doxorubicin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yueling Yuan,1,* Tiange Cai,2,* Richard Callaghan,3,* Qianwen Li,4 Yinghong Huang,4 Bingyue Wang,1 Qingqing Huang,1 Manling Du,1 Qianqian Ma,1 Peter Chiba,5 Yu Cai1,6 1College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China; 2College of Life Science, Liaoning University, Shenyang, Liaoning 110000, China; 3Research School of Biology, Australian National University, Canberra ACT 2601, Australia; 4Guangzhou Guoyu Pharmaceutical Technology Co., Ltd., Guangzhou, Guangdong 510663, China; 5Institute of Medical Chemistry, Medical University of Vienna, Vienna 1090, Austria; 6Cancer Research Institute, Jinan University, Guangzhou, Guangdong 510632, China *These authors contributed equally to this work Background: Psoralen (PSO), a major active component of Psoralea corylifolia, has been shown to overcome multidrug resistance in cancer. A drug carrier comprising a lipid-monolayer shell and a biodegradable polymer core for sustained delivery and improved efficacy of drug have exhibited great potential in efficient treatment of cancers.Methods: The PSO-loaded lipid polymer hybrid nanoparticles were prepared and characterized. In vitro cytotoxicity assay, cellular uptake, cell cycle analysis, detection of ROS level and mitochondrial membrane potential (ΔΨm) and western blot were performed. Results: The P-LPNs enhanced the cytotoxicity of doxorubicin (DOX) 17-fold compared to free DOX in multidrug resistant HepG2/ADR cells. Moreover, P-LPNs displayed pro-apoptotic activity, increased levels of ROS and depolarization of ΔΨm. In addition, there were no significant effects on cellular uptake of DOX, cell cycle arrest, or the expression of P-glycoprotein. Mechanistic studies suggested that P-LPNs enhanced DOX cytotoxicity by increased release of cytochrome c and enhanced caspase3 cleavage, causing apoptosis in HepG2/ADR cells.Conclusion: The lipid-polymer hybrid nanoparticles can be considered a powerful and promising drug delivery system for effective cancer chemotherapy. Keywords: lipid-polymer hybrid nanoparticles, psoralen, drug delivery, HepG2, ADR cells, apoptosis  Yuan YCai TCallaghan RLi QHuang YWang BHuang QDu MMa QChiba PCai YDove Medical PressarticleLipid-polymer hybrid nanoparticlespsoralendrug deliveryHepG2/ADR cellsapoptosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2207-2218 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lipid-polymer hybrid nanoparticles psoralen drug delivery HepG2/ADR cells apoptosis Medicine (General) R5-920
spellingShingle	Lipid-polymer hybrid nanoparticles psoralen drug delivery HepG2/ADR cells apoptosis Medicine (General) R5-920 Yuan Y Cai T Callaghan R Li Q Huang Y Wang B Huang Q Du M Ma Q Chiba P Cai Y Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
description	Yueling Yuan,1,* Tiange Cai,2,* Richard Callaghan,3,* Qianwen Li,4 Yinghong Huang,4 Bingyue Wang,1 Qingqing Huang,1 Manling Du,1 Qianqian Ma,1 Peter Chiba,5 Yu Cai1,6 1College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China; 2College of Life Science, Liaoning University, Shenyang, Liaoning 110000, China; 3Research School of Biology, Australian National University, Canberra ACT 2601, Australia; 4Guangzhou Guoyu Pharmaceutical Technology Co., Ltd., Guangzhou, Guangdong 510663, China; 5Institute of Medical Chemistry, Medical University of Vienna, Vienna 1090, Austria; 6Cancer Research Institute, Jinan University, Guangzhou, Guangdong 510632, China *These authors contributed equally to this work Background: Psoralen (PSO), a major active component of Psoralea corylifolia, has been shown to overcome multidrug resistance in cancer. A drug carrier comprising a lipid-monolayer shell and a biodegradable polymer core for sustained delivery and improved efficacy of drug have exhibited great potential in efficient treatment of cancers.Methods: The PSO-loaded lipid polymer hybrid nanoparticles were prepared and characterized. In vitro cytotoxicity assay, cellular uptake, cell cycle analysis, detection of ROS level and mitochondrial membrane potential (ΔΨm) and western blot were performed. Results: The P-LPNs enhanced the cytotoxicity of doxorubicin (DOX) 17-fold compared to free DOX in multidrug resistant HepG2/ADR cells. Moreover, P-LPNs displayed pro-apoptotic activity, increased levels of ROS and depolarization of ΔΨm. In addition, there were no significant effects on cellular uptake of DOX, cell cycle arrest, or the expression of P-glycoprotein. Mechanistic studies suggested that P-LPNs enhanced DOX cytotoxicity by increased release of cytochrome c and enhanced caspase3 cleavage, causing apoptosis in HepG2/ADR cells.Conclusion: The lipid-polymer hybrid nanoparticles can be considered a powerful and promising drug delivery system for effective cancer chemotherapy. Keywords: lipid-polymer hybrid nanoparticles, psoralen, drug delivery, HepG2, ADR cells, apoptosis
format	article
author	Yuan Y Cai T Callaghan R Li Q Huang Y Wang B Huang Q Du M Ma Q Chiba P Cai Y
author_facet	Yuan Y Cai T Callaghan R Li Q Huang Y Wang B Huang Q Du M Ma Q Chiba P Cai Y
author_sort	Yuan Y
title	Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
title_short	Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
title_full	Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
title_fullStr	Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
title_full_unstemmed	Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells
title_sort	psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant hepg2 cells
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/54881fbd6ddb4cd285b70a4c68b2e85a
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Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells

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