Synthesis and cellular uptake mechanism of Tat decorated Au/Au2S nanoparticles
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摘要: 为了实现对肿瘤的靶向性药物/基因治疗,通过化学还原法制备了细胞穿膜肽Tat修饰的Au-Au2S纳米药物载体。采用透射电镜、表面增强拉曼光谱仪、紫外分光光度计对Tat/Au-Au2S纳米粒子进行表征,采用流式细胞仪、激光共聚焦显微镜研究Tat/Au-Au2S纳米粒子的穿细胞膜机制。理化分析结果表明,Tat可通过Au—S键接枝于Au-Au2S纳米粒子表面, 直径约50 nm的Tat/Au-Au2S纳米粒子具有近红外敏感性。细胞内化途径示踪物共定位分析和抑制剂阻断实验表明, Tat/Au-Au2S纳米粒子以脂筏介导的巨胞饮途径进入Hela细胞, 而以受体和脂筏共介导的巨胞饮途径进入骨髓间充质干细胞(BMSCs)。Abstract: To realize an efficient and targeted cancer therapy by the drug/gene carrier, cell penetrating peptide Tat decorated Au-Au2S nanoparticles were prepared by a redox method. Transmission electron microscopy (TEM), surface enhanced Raman scattering (SERS) and UV-vis spectrometer were used for characterizing Tat/Au-Au2S nanoparticles, and confocal laser scanning microscope (CLSM) and flow cytometer (FACS) were used to investigate the mechanism of cellular uptake. The chemicophysical results indicate that Tat peptide could be conjugated onto Au Au2S nanoparticles via Au—S bonds, and Tat/Au-Au2S nanoparticles present as 50 nm-diameter sphericities with NIR sensitivity. Co-location and endocytosis inhibition experiments suggest that Tat/Au-Au2S nanoparticles may enter Hela cells via a lipid raft mediated endocytosis pathway, whereas via a combined endocytosis pathway of lipid raft-dependent and receptor-dependent into bone marrow stromal cells (BMSCs).
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Key words:
- Au-Au2S /
- drug nano-carrier /
- Tat peptide /
- cell uptake mechanism
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