Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles.
Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles.
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DOI：
10.2147/ijn.s145326
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发表时间：
2017
影响因子：
8
通讯作者：
Narayanaswami V
中科院分区：
文献类型：
--
作者：
Chuang ST;Shon YS;Narayanaswami V
我们已经开发了一种基于高密度脂蛋白（HDL）的平台，用于运输和递送疏水性金纳米颗粒（AuNPs）。利用载脂蛋白E3（apoE 3）作为低密度脂蛋白受体（LDLr）的高亲和力配体的能力来获得HDL与AuNPs进入胶质母细胞瘤细胞。通过与磷脂和apoE 3整合来溶解直径为3、10和17 nm的AuNPs（后两者通过相转移过程合成），从而产生携带AuNPs的重构HDL（rHDL）。紫外-可见光谱表明rHDL-AuNP的稳定颗粒的存在下，在约530 nm的表面等离子体带。rHDL-AuNP的透射电子显微镜（TEM）显示具有包埋在核心中的AuNP的大致球形颗粒。rHDL-AuNP颗粒显示出与LDLr的稳健结合，并通过胶质母细胞瘤细胞中受体介导的内吞作用内化。共聚焦显微镜证实细胞摄取的金纳米粒子的内体-溶酶体室，而TEM显示细胞内聚集的金纳米粒子。细胞活力测定表明，0.1-100 μg/mL的rHDL-AuNP处理24小时后，>85%的细胞存活。这些发现是重要的，因为它们提供了跨细胞膜递送AuNP的有效手段，这在过表达LDLr的肿瘤细胞中特别相关。
We have developed a high-density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration with phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs. Ultraviolet–visible spectra of rHDL-AuNP indicated the presence of stable particles with surface plasmon band at ~530 nm. Transmission electron microscopy (TEM) of rHDL-AuNP revealed roughly spherical particles with AuNPs embedded in the core. The rHDL-AuNP particles displayed robust binding to the LDLr and were internalized by receptor-mediated endocytosis in glioblastoma cells. Confocal microscopy confirmed cellular uptake of AuNPs in the endosomal–lysosomal compartments, while TEM revealed intracellular aggregated AuNPs. Cell viability assay demonstrated that >85% of cells were viable with rHDL-AuNP treatment of 0.1–100 μg/mL for 24 hours. These findings are significant since they offer an effective means of delivering AuNPs across the cell membrane, which is particularly relevant in tumor cells that overexpress LDLr.