Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice.

Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice.
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DOI:
10.1016/j.biomaterials.2008.12.038
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发表时间:
2009-04
期刊:
影响因子:
14
通讯作者:
Li, Chun
Li, Chun
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhang, Guodong;Yang, Zhi;Lu, Wei;Zhang, Rui;Huang, Qian;Tian, Mei;Li, Li;Liang, Dong;Li, Chun

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聚乙二醇(PEG)包覆的(聚乙二醇化的)金纳米颗粒(AuNPs)已被提议作为药物载体和诊断造影剂。然而,颗粒特性对聚乙二醇化金纳米颗粒的生物分布和药代动力学的影响尚不清楚。我们研究了PEG分子量、锚定配体的类型和粒径对PEG包覆的金纳米粒子的组装性能和胶体稳定性的影响。采用111 In标记的金纳米粒子进一步研究了最稳定的PEG包被的金纳米粒子在荷A431鳞状细胞癌裸鼠体内的药代动力学和生物分布。在二硫苏糖醇存在下,用硫辛酸(TA)锚定的PEG涂覆的金纳米颗粒在磷酸盐缓冲盐水中表现出比用单硫醇锚定的PEG涂覆的金纳米颗粒更高的胶体稳定性。用高分子量(5000 Da)PEG包被的金纳米颗粒比用低分子量(2000 Da)PEG包被的金纳米颗粒更稳定。在用TA封端的PEG 5000包被的20-nm、40-nm和80-nm AuNP中,20-nm AuNP表现出由网状内皮细胞的最低摄取和从身体的最慢清除。此外,与40-和80-nm AuNP相比,用TA-终止的PEG 5000涂覆的20-nm AuNP显示出显著更高的肿瘤摄取和从肿瘤血管的外渗。因此,20-nm的金纳米粒子涂有TA封端的PEG 5000是有前途的潜在的药物输送车辆和诊断成像剂。
Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using 111In-labeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiol-anchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEG5000, the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEG5000 showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40- and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG5000 are promising potential drug delivery vehicles and diagnostic imaging agents.
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期刊: BIOMACROMOLECULES
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