Uptake Mechanism and Endosomal Fate of Drug-Phospholipid Lipid Nanoparticles in Subcutaneous and In Situ Hepatoma
Uptake Mechanism and Endosomal Fate of Drug-Phospholipid Lipid Nanoparticles in Subcutaneous and In Situ Hepatoma
复制标题
药物-磷脂纳米颗粒在皮下和原位肝癌中的摄取机制和内体命运
DOI：
10.1166/jbn.2014.1776
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发表时间：
2014-06-01
影响因子：
2.9
通讯作者：
Zhang, Zhirong
中科院分区：
文献类型：
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作者：
Wang, Qi;Liu, Peifeng;Zhang, Zhirong
药物-磷脂脂质纳米粒（DPLN）可以有效地增强传统固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC）的性质，正如我们的研究小组和其他人之前所证明的那样。然而，迄今为止，很少有研究集中在细胞摄取机制和DPLN在肝癌中的命运。因此，我们通过体外和体内实验系统地研究了DPLN的细胞摄取机制和内体命运。共聚焦激光扫描显微镜（CLSM）和流式细胞术证明Raw 264.7细胞系（巨噬细胞Raw 264.7细胞）、Chang细胞（人肝细胞系）和HepG 2细胞（人肝癌细胞系）表现出不同的摄取机制。Raw 264.7细胞用作检查肝靶向能力的模型。来自皮下肝癌和原位肝癌小鼠的结果证实了DPLN的肝肿瘤靶向性质与肝脏药物储库功能相关。这些发现进一步提高了我们对DPLN临床应用的理解。
Drug-phospholipid lipid nanoparticles (DPLNs) can effectively enhance the properties of traditional solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), as previously demonstrated by our research group and others. To date, however, very few studies have focused on the cellular uptake mechanism and fate of DPLNs in hepatoma. Therefore, we systematically studied the cellular uptake mechanism and endosomal fate of DPLNs through in vitro and in vivo experiments. Confocal laser scanning microscopy (CLSM) and flow cytometry demonstrated that the Raw264.7 cell line (macrophage Raw264.7 cells), Chang cells (a human liver cell line) and HepG2 cells (a human hepatoma cell line) exhibited distinct uptake mechanisms. The Raw264.7 cells served as a model for examining liver-targeting ability. The results from mice with subcutaneous hepatomas and in situ hepatomas confirmed that the liver tumor-targeting property of the DPLNs was associated with the liver drug reservoir function. These findings further improve our understanding of DPLNs for clinical applications.