Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction

Cancheng Liao,* Danqiao Xu,* Xiaohong Liu, Yuqi Fang, Jun Yi, Xiaofang Li, Bohong Guo Department of Pharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China *These authors contributed equally to this work Background and aim: Iridium (Ir)-based complex is a potential antitumor...

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Autores principales:	Liao C, Xu D, Liu X, Fang Y, Yi J, Li X, Guo B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Iridium complex liposome Apoptosis reactive oxygen species mitochondria Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/70cfe478c06d4f809a2f11f231b39838
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spelling	oai:doaj.org-article:70cfe478c06d4f809a2f11f231b398382021-12-02T00:22:55ZIridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction1178-2013https://doaj.org/article/70cfe478c06d4f809a2f11f231b398382018-07-01T00:00:00Zhttps://www.dovepress.com/iridium-iii-complex-loaded-liposomes-as-a-drug-delivery-system-for-lun-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cancheng Liao,* Danqiao Xu,* Xiaohong Liu, Yuqi Fang, Jun Yi, Xiaofang Li, Bohong Guo Department of Pharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China *These authors contributed equally to this work Background and aim: Iridium (Ir)-based complex is a potential antitumor ingredient, but its poor physicochemical properties such as hydrophobicity and low biocompatibility hamper further application. Liposome provides a potential delivery approach for improving the poor physicochemical property and reducing the side effects of antitumor drug. In this study, we aimed at incorporating Ir ([Ir(ppy)2(BTCP)]PF6) into liposomes to enhance the biocompatibility and sustained release of Ir for intravenous administration and to elucidate the mechanism in A549 cells. Materials and methods: Ir-loaded PEGylated liposomes (Lipo-Ir) were formulated by thin-film dispersion and ultrasonic method. Morphology, size distribution, and zeta potential of Lipo-Ir were examined by transmission electron microscopy (TEM) and Zetasizer. The released profile and biocompatibility were investigated by dialysis method and hemolysis test, respectively. Additionally, the cytotoxic activity and mechanism of Lipo-Ir and Ir inducing apoptosis in A549 cells were evaluated. Results: Lipo-Ir can keep sustained release, excellent biocompatibility, and physical stability. The average particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading are 112.57±1.15 nm, 0.19±0.02, -10.66±0.61 mV, 94.71%±3.21%, and 4.71%±0.41%, respectively. 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) assay show that Lipo-Ir and Ir display high cytotoxicity against selected cancer cells. Furthermore, the apoptotic features of morphology, depolarization of mitochondrial membrane potential, increase in the reactive oxygen species (ROS) levels, and disorder of Ca2+ homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G0/G1 phase. Conclusion: The studies demonstrate that Lipo-Ir can trigger apoptosis in A549 cells via ROS-mediated mitochondrial dysfunctions, and the biocompatible and sustained Lipo-Ir will be a promising drug delivery system. Keywords: iridium complex, liposome, apoptosis, reactive oxygen species, mitochondriaLiao CXu DLiu XFang YYi JLi XGuo BDove Medical PressarticleIridium complexliposomeApoptosisreactive oxygen speciesmitochondriaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4417-4431 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Iridium complex liposome Apoptosis reactive oxygen species mitochondria Medicine (General) R5-920
spellingShingle	Iridium complex liposome Apoptosis reactive oxygen species mitochondria Medicine (General) R5-920 Liao C Xu D Liu X Fang Y Yi J Li X Guo B Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
description	Cancheng Liao,* Danqiao Xu,* Xiaohong Liu, Yuqi Fang, Jun Yi, Xiaofang Li, Bohong Guo Department of Pharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China *These authors contributed equally to this work Background and aim: Iridium (Ir)-based complex is a potential antitumor ingredient, but its poor physicochemical properties such as hydrophobicity and low biocompatibility hamper further application. Liposome provides a potential delivery approach for improving the poor physicochemical property and reducing the side effects of antitumor drug. In this study, we aimed at incorporating Ir ([Ir(ppy)2(BTCP)]PF6) into liposomes to enhance the biocompatibility and sustained release of Ir for intravenous administration and to elucidate the mechanism in A549 cells. Materials and methods: Ir-loaded PEGylated liposomes (Lipo-Ir) were formulated by thin-film dispersion and ultrasonic method. Morphology, size distribution, and zeta potential of Lipo-Ir were examined by transmission electron microscopy (TEM) and Zetasizer. The released profile and biocompatibility were investigated by dialysis method and hemolysis test, respectively. Additionally, the cytotoxic activity and mechanism of Lipo-Ir and Ir inducing apoptosis in A549 cells were evaluated. Results: Lipo-Ir can keep sustained release, excellent biocompatibility, and physical stability. The average particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading are 112.57±1.15 nm, 0.19±0.02, -10.66±0.61 mV, 94.71%±3.21%, and 4.71%±0.41%, respectively. 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) assay show that Lipo-Ir and Ir display high cytotoxicity against selected cancer cells. Furthermore, the apoptotic features of morphology, depolarization of mitochondrial membrane potential, increase in the reactive oxygen species (ROS) levels, and disorder of Ca2+ homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G0/G1 phase. Conclusion: The studies demonstrate that Lipo-Ir can trigger apoptosis in A549 cells via ROS-mediated mitochondrial dysfunctions, and the biocompatible and sustained Lipo-Ir will be a promising drug delivery system. Keywords: iridium complex, liposome, apoptosis, reactive oxygen species, mitochondria
format	article
author	Liao C Xu D Liu X Fang Y Yi J Li X Guo B
author_facet	Liao C Xu D Liu X Fang Y Yi J Li X Guo B
author_sort	Liao C
title	Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title_short	Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title_full	Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title_fullStr	Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title_full_unstemmed	Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title_sort	iridium (iii) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/70cfe478c06d4f809a2f11f231b39838
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Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction

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