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巯基化和聚乙二醇化有机硅纳米粒子的体外和体内毒性。

In vitro and in vivo toxicity of thiolated and PEGylated organosilica nanoparticles.

机构信息

School of Engineering and Digital Science, Nazarbayev University, 010000 Astana, Kazakhstan; School of Sciences and Humanities, Nazarbayev University, 010000 Astana, Kazakhstan.

School of Sciences and Humanities, Nazarbayev University, 010000 Astana, Kazakhstan.

出版信息

Int J Pharm. 2024 Mar 5;652:123852. doi: 10.1016/j.ijpharm.2024.123852. Epub 2024 Jan 26.

DOI:10.1016/j.ijpharm.2024.123852
PMID:38280501
Abstract

This study comprises the comprehensive toxicological assessment of thiolated organosilica nanoparticles (NPs) synthesised from 3-mercaptopropyltrimethoxysilane (MPTS). We investigated the influence of three different types of nanoparticles synthesised from 3-mercaptopropyltrimethoxysilane: the starting thiolated silica (Si-NP-SH) and their derivatives prepared by surface PEGylation with PEG 750 (Si-NP-PEG750) and 5000 Da (Si-NP-PEG5000) on biological subjects from in vitro to in vivo experiments to explore the possible applications of those nanoparticles in biomedical research. As a result of this study, we generated a comprehensive understanding of the toxicological properties of these nanoparticles, including their cytotoxicity in different cell lines, hemolytic properties, in vitro localisation, mucosal irritation properties and biodistribution in BALB/c mice. Our findings indicate that all three types of nanoparticles can be considered safe and have promising prospects for use in biomedical applications. Nanoparticles did not affect the viability of HPF, MCF7, HEK293 and A549 cell lines at low concentrations (up to 100 µg/mL); moreover, they did not cause organ damage to BALB/c mice at concentrations of 10 mg/kg. The outcomes of this study enhance our understanding of the impact of organosilica nanoparticles on health and the environment, which is vital for developing silica nanoparticle-based drug delivery systems and provides opportunities to expand the applications of organosilica nanoparticles.

摘要

本研究对由 3-巯丙基三甲氧基硅烷(MPTS)合成的硫醇化有机硅纳米粒子(NPs)进行了全面的毒理学评估。我们研究了三种不同类型的由 3-巯丙基三甲氧基硅烷合成的纳米粒子的影响:起始硫醇化硅(Si-NP-SH)及其通过表面 PEG 化分别用 PEG 750(Si-NP-PEG750)和 5000 Da(Si-NP-PEG5000)制备的衍生物,从体外到体内实验,探索这些纳米粒子在生物医学研究中的可能应用。通过这项研究,我们全面了解了这些纳米粒子的毒理学特性,包括它们在不同细胞系中的细胞毒性、溶血特性、体外定位、粘膜刺激性和在 BALB/c 小鼠中的生物分布。我们的研究结果表明,所有三种类型的纳米粒子都可以被认为是安全的,并且在生物医学应用中有广阔的应用前景。在低浓度(高达 100μg/ml)时,三种类型的纳米粒子都不会影响 HPF、MCF7、HEK293 和 A549 细胞系的活力;此外,在 10mg/kg 的浓度下,它们也不会对 BALB/c 小鼠造成器官损伤。这项研究的结果增强了我们对有机硅纳米粒子对健康和环境影响的认识,这对于开发基于硅纳米粒子的药物输送系统至关重要,并为有机硅纳米粒子的应用提供了机会。

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