Cellular distribution of injected PLGA-nanoparticles in the liver.
Cellular distribution of injected PLGA-nanoparticles in the liver.
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DOI：
10.1016/j.nano.2016.01.013
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Iwakiri Y
中科院分区：
文献类型：
--
作者：
Park JK;Utsumi T;Seo YE;Deng Y;Satoh A;Saltzman WM;Iwakiri Y
纳米颗粒在肝脏中的细胞命运尚未完全了解。由于纳米颗粒在肝脏治疗中的有效性和安全性取决于将纳米颗粒靶向正确的细胞群，因此本研究旨在确定PLGA纳米颗粒（尺寸为271±1.4 nm）在体内肝细胞中的相对分布。我们发现枯否细胞是摄取纳米颗粒的主要细胞，其次是肝窦内皮细胞和肝星状细胞。仅在7%的肝细胞中发现了纳米颗粒。通过氯膦酸盐脂质体消耗枯否细胞增加了纳米颗粒在肝窦内皮细胞和肝星状细胞中的滞留，但在肝细胞中没有。重要的是，载药纳米颗粒递送至肝脏的研究必须证明不仅靶细胞类型吸收纳米颗粒，而且其他细胞类型不吸收纳米颗粒，以评估其效果并确保其安全性。肝脏中纳米颗粒摄取的总结。在肝细胞中观察到纳米颗粒（NP）摄取的层次结构，其特征在于库普弗细胞占主导地位，其次是肝窦内皮细胞（LSEC）、肝星状细胞（HSC）和有限的肝细胞进入。
The cellular fate of nanoparticles in the liver is not fully understood. Because the effectiveness and safety of nanoparticles in liver therapy depends on targeting nanoparticles to the right cell populations, this study aimed to determine a relative distribution of PLGA-nanoparticles (sizes 271±1.4 nm) among liver cells in vivo. We found that Kupffer cells were the major cells that took up nanoparticles, followed by liver sinusoidal endothelial cells and hepatic stellate cells. Nanoparticles were found in only 7% of hepatocytes. Depletion of Kupffer cells by clodronate liposomes increased nanoparticle retention in liver sinusoidal endothelial cells and hepatic stellate cells, but not in hepatocytes. It is importantly suggested that studies of drug-loaded nanoparticle delivery to the liver have to demonstrate not only uptake of nanoparticles by the target cell type but also non-uptake by other cell types to assess their effect as well as ensure their safety. Summary of nanoparticle uptake in the liver. A hierarchy of nanoparticle (NP) uptake is seen among liver cells, which is characterized by dominance of Kupffer cells, followed by liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), and limited access to hepatocytes.