International Journal of Nanomedicine (May 2019)
Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
Abstract
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
