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金纳米颗粒的药代动力学、生物分布及毒性的形状和尺寸依赖性

Shape and Size Dependence of Pharmacokinetics, Biodistribution, and Toxicity of Gold Nanoparticles.

作者信息

Wu Huaping, Tang Lin, Dong Huanhuan, Zhi Maoxin, Guo Liqiong, Hong Xuechuan, Liu Mingzhe, Xiao Yuling, Zeng Xiaodong

机构信息

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China.

出版信息

Mol Pharm. 2025 Jan 6;22(1):196-208. doi: 10.1021/acs.molpharmaceut.4c00832. Epub 2024 Nov 26.

DOI:10.1021/acs.molpharmaceut.4c00832
PMID:39589203
Abstract

Gold nanoparticles (AuNPs) are extensively utilized in biomolecular sensing, photothermal therapy, drug delivery, and various imaging techniques like photoacoustic and fluorescent imaging. Despite their diverse applications, inconsistent findings from previous toxicity studies underscore the critical need for standardized methodologies. This study introduces ten distinct types of AuNPs─cubes, stars, rods, dumbbells, and bipyramids at sizes of 50 and 100 nm, to systematically assess their toxicity under controlled conditions both and . Our findings reveal a clear correlation between cytotoxicity and the morphology, size, incubation duration, and concentration of AuNPs. Anisotropically shaped nanoparticles, such as nanorods, nanodumbbells, and nanobipyramids, tend to exhibit higher cytotoxicity compared to more spherical forms like nanocubes and nanostars. Interestingly, while plasma biochemistry parameters show minimal variation, biodistribution, histopathological alterations, and pharmacokinetics are notably influenced by the shape and size of AuNPs. In most instances, smaller and anisotropic AuNPs that remain in the bloodstream for extended periods are observed. This research offers significant insights into the design of AuNPs with specific morphologies and sizes, particularly for their application in drug delivery systems intravenous injection. These outcomes emphasize the nuanced toxicity profiles of AuNPs, necessitating tailored approaches in preclinical and clinical research.

摘要

金纳米颗粒(AuNPs)被广泛应用于生物分子传感、光热疗法、药物递送以及多种成像技术,如光声成像和荧光成像。尽管其应用广泛,但以往毒性研究结果不一致,凸显了标准化方法的迫切需求。本研究引入了十种不同类型的金纳米颗粒——尺寸为50纳米和100纳米的立方体、星形、棒形、哑铃形和双锥体,以在可控条件下系统评估它们的毒性。我们的研究结果揭示了细胞毒性与金纳米颗粒的形态、尺寸、孵育时间和浓度之间存在明显的相关性。与纳米立方体和纳米星形等更球形的形式相比,各向异性形状的纳米颗粒,如纳米棒、纳米哑铃和纳米双锥体,往往表现出更高的细胞毒性。有趣的是,虽然血浆生化参数变化最小,但生物分布、组织病理学改变和药代动力学受到金纳米颗粒形状和尺寸的显著影响。在大多数情况下,观察到较小的各向异性金纳米颗粒会在血液中长时间停留。这项研究为设计具有特定形态和尺寸的金纳米颗粒提供了重要见解,特别是在静脉注射药物递送系统中的应用。这些结果强调了金纳米颗粒细微的毒性特征,在临床前和临床研究中需要采用针对性的方法。

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