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

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...

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Autores principales: Liao, Cancheng, Xu, Danqiao, Liu, Xiaohong, Fang, Yuqi, Yi, Jun, Li, Xiaofang, Guo, Bohong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071621/
https://www.ncbi.nlm.nih.gov/pubmed/30104875
http://dx.doi.org/10.2147/IJN.S170035
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author Liao, Cancheng
Xu, Danqiao
Liu, Xiaohong
Fang, Yuqi
Yi, Jun
Li, Xiaofang
Guo, Bohong
author_facet Liao, Cancheng
Xu, Danqiao
Liu, Xiaohong
Fang, Yuqi
Yi, Jun
Li, Xiaofang
Guo, Bohong
author_sort Liao, Cancheng
collection PubMed
description 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)]PF(6)) 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 Ca(2+) homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G(0)/G(1) 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.
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spelling pubmed-60716212018-08-13 Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction Liao, Cancheng Xu, Danqiao Liu, Xiaohong Fang, Yuqi Yi, Jun Li, Xiaofang Guo, Bohong Int J Nanomedicine Original Research 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)]PF(6)) 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 Ca(2+) homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G(0)/G(1) 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. Dove Medical Press 2018-07-30 /pmc/articles/PMC6071621/ /pubmed/30104875 http://dx.doi.org/10.2147/IJN.S170035 Text en © 2018 Liao et al. 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.
spellingShingle Original Research
Liao, Cancheng
Xu, Danqiao
Liu, Xiaohong
Fang, Yuqi
Yi, Jun
Li, Xiaofang
Guo, Bohong
Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer through mitochondrial dysfunction
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071621/
https://www.ncbi.nlm.nih.gov/pubmed/30104875
http://dx.doi.org/10.2147/IJN.S170035
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