Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
Solid lipid nanoparticle induced apoptosis of macrophages via a mitochondrial-dependent pathway in vitro and in vivo
复制标题
固体脂质纳米颗粒通过体外和体内线粒体依赖性途径诱导巨噬细胞凋亡
DOI：
10.2147/ijn.s200395
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Tang, He-Bin
中科院分区：
文献类型：
--
作者：
Liang, Wan-Li;Xiao, Lan;Tang, He-Bin
背景和目的：脂质纳米粒因其具有稳定亲脂性和亲水性分子的作用而被广泛应用于药物释放系统。LN通常被认为对于体内应用是相当安全和方便的。然而，我们以前观察到某些类型的LN可能会导致枯否细胞的损失，枯否细胞是肝脏中的一种常驻巨噬细胞。因此，我们研究了这种现象的细节。研究方法：MTT法、Annexin-V-FITC/PI双染、JC-1染色、流式细胞术、Western blot和透射电镜等方法进行细胞基础实验。另外，采用血清生化分析、H&E染色和免疫荧光染色等方法检测小鼠肝组织标本中组织结构的急、慢性变化和枯否细胞的数量。结果：LN可使Raw 264. 7细胞线粒体去极化、肿胀，Bax/Bcl-2平衡紊乱。这导致caspase-3和PARP的切割和激活，然后诱导Raw 264. 7细胞凋亡。此外，无论是急性或慢性应用LN都足以破坏小鼠肝门静脉的结构，并减少枯否细胞的数量。结论：LNs可诱导巨噬细胞凋亡，凋亡途径依赖于细胞凋亡。
Background 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.