Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo

Wan-Li Liang,1,* Lan Xiao,2,* Hong-Wei Gu,1 Xiao-Jun Li,1 Yu-Sang Li,1 Wei Kevin Zhang,1 He-Bin Tang11School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, People’s Republic of China; 2Department of Traditional Chinese Medicine, Third Xiangya Hospital...

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Autores principales: Liang WL, Xiao L, Gu HW, Li XJ, Li YS, Zhang WK, Tang HB
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Lenguaje:EN
Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:f95b772367454d9aaff9c39026a604562021-12-02T10:53:13ZSolid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo1178-2013https://doaj.org/article/f95b772367454d9aaff9c39026a604562019-05-01T00:00:00Zhttps://www.dovepress.com/solid-lipid-nanoparticlenbspinduced-apoptosis-of-macrophages-via-a-mit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wan-Li Liang,1,* Lan Xiao,2,* Hong-Wei Gu,1 Xiao-Jun Li,1 Yu-Sang Li,1 Wei Kevin Zhang,1 He-Bin Tang11School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, People’s Republic of China; 2Department of Traditional Chinese Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, People’s Republic of China *These authors contributed equally to this workBackground and aims: Lipid nanoparticles (LNs) are widely applied in drug delivery systems because they can incorporate and stabilize lipophilic and hydrophilic molecules. LNs are generally considered quite safe and convenient for in vivo applications. However, we previously observed that certain types of LNs could cause a loss of Kupffer cells, a kind of resident macrophage in the liver. As a result, we investigated the details of this phenomenon.Methods: MTT assay, Annexin-V-FITC/PI double staining, JC-1 staining, flow cytometry, Western blot and transmission electron microscopy were used in cell-based experiments. Additionally, serum biochemical analyses, H&E staining and immunofluorescence staining were performed to detect the acute and chronic changes of tissue structure and the number of Kupffer cells in mouse liver tissue samples.Results: Application of LN depolarized and swelled the mitochondria of Raw264.7 cells, and disrupted the balance of Bax/Bcl-2. This led to cleavage and activation of caspase-3 and PARP, and then induced apoptosis of Raw264.7 cells. In addition, either acute or chronic applications of LN were sufficient to disrupt the structure of the hepatic portal vein and reduce the number of Kupffer cells in mice.Conclusions: LNs could induce apoptosis of macrophages through a mitochondrial-dependent pathway.Keywords: Lipidic nanocarrier, cell death, macrophages in liver, Bax/Bcl-2, Caspase-3Liang WLXiao LGu HWLi XJLi YSZhang WKTang HBDove Medical PressarticleLipidic nanocarrierCell deathMacrophages in liverBax/Bcl-2Caspase-3;Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3283-3295 (2019)
institution DOAJ
collection DOAJ
language EN
topic Lipidic nanocarrier
Cell death
Macrophages in liver
Bax/Bcl-2
Caspase-3;
Medicine (General)
R5-920
spellingShingle Lipidic nanocarrier
Cell death
Macrophages in liver
Bax/Bcl-2
Caspase-3;
Medicine (General)
R5-920
Liang WL
Xiao L
Gu HW
Li XJ
Li YS
Zhang WK
Tang HB
Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
description Wan-Li Liang,1,* Lan Xiao,2,* Hong-Wei Gu,1 Xiao-Jun Li,1 Yu-Sang Li,1 Wei Kevin Zhang,1 He-Bin Tang11School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, People’s Republic of China; 2Department of Traditional Chinese Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, People’s Republic of China *These authors contributed equally to this workBackground and aims: Lipid nanoparticles (LNs) are widely applied in drug delivery systems because they can incorporate and stabilize lipophilic and hydrophilic molecules. LNs are generally considered quite safe and convenient for in vivo applications. However, we previously observed that certain types of LNs could cause a loss of Kupffer cells, a kind of resident macrophage in the liver. As a result, we investigated the details of this phenomenon.Methods: MTT assay, Annexin-V-FITC/PI double staining, JC-1 staining, flow cytometry, Western blot and transmission electron microscopy were used in cell-based experiments. Additionally, serum biochemical analyses, H&E staining and immunofluorescence staining were performed to detect the acute and chronic changes of tissue structure and the number of Kupffer cells in mouse liver tissue samples.Results: Application of LN depolarized and swelled the mitochondria of Raw264.7 cells, and disrupted the balance of Bax/Bcl-2. This led to cleavage and activation of caspase-3 and PARP, and then induced apoptosis of Raw264.7 cells. In addition, either acute or chronic applications of LN were sufficient to disrupt the structure of the hepatic portal vein and reduce the number of Kupffer cells in mice.Conclusions: LNs could induce apoptosis of macrophages through a mitochondrial-dependent pathway.Keywords: Lipidic nanocarrier, cell death, macrophages in liver, Bax/Bcl-2, Caspase-3
format article
author Liang WL
Xiao L
Gu HW
Li XJ
Li YS
Zhang WK
Tang HB
author_facet Liang WL
Xiao L
Gu HW
Li XJ
Li YS
Zhang WK
Tang HB
author_sort Liang WL
title Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
title_short Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
title_full Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
title_fullStr Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
title_full_unstemmed Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
title_sort solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/f95b772367454d9aaff9c39026a60456
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