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染料掺杂的可生物降解纳米粒子 SiO 涂层在氧化锌和氧化铁纳米粒子上,以提高生物相容性和用于体内成像研究。

Dye-doped biodegradable nanoparticle SiO coating on zinc- and iron-oxide nanoparticles to improve biocompatibility and for in vivo imaging studies.

机构信息

Dpto. de Física Aplicada, Universidad de Cantabria, Facultad de Ciencias, 39005 Santander, Spain.

出版信息

Nanoscale. 2020 Mar 14;12(10):6164-6175. doi: 10.1039/c9nr08743e. Epub 2020 Mar 5.

Abstract

In vivo imaging and therapy represent one of the most promising areas in nanomedicine. Particularly, the identification and localization of nanomaterials within cells and tissues are key issues to understand their interaction with biological components, namely their cell internalization route, intracellular destination, therapeutic activity and possible cytotoxicity. Here, we show the development of multifunctional nanoparticles (NPs) by providing luminescent functionality to zinc and iron oxide NPs. We describe simple synthesis methods based on modified Stöber procedures to incorporate fluorescent molecules on the surface of oxide NPs. These procedures involve the successful coating of NPs with size-controlled amorphous silica (SiO) shells incorporating standard chromophores like fluorescein, rhodamine B or rhodamine B isothiocyanate. Specifically, spherical FeO NPs with an average size of 10 nm and commercial ZnO NPs (ca. 130 nm), both coated with an amorphous SiO shell of ca. 15 and 24 nm thickness, respectively, are presented. The magnetic nanoparticles, with a major presence of magnetite, show negligible coercitivity. Hence, interactions (dipolar) are very weak and the cores are in the superparamagnetic regime. Spectroscopic measurements confirm the presence of fluorescent molecules within the SiO shell, making these hybrid NPs suitable for bioimaging. Thus, our coating procedures improve NP dispersibility in physiological media and allow the identification and localization of intracellular ZnO and FeO NPs using confocal microscopy imaging preserving the fluorescence of the NP. We demonstrate how both FeO and ZnO NPs coated with luminescent SiO are internalized and accumulated in the cell cytoplasm after 24 hours. Besides, the SiO shell provides a platform for further functionalization that enables the design of targeted therapeutic strategies. Finally, we studied the degradation of the shell in different physiological environments, pointing out that the SiO coating is stable enough to reach the target cells maintaining its original structure. Degradation took place only 24 hours after exposure to different media.

摘要

体内成像和治疗代表了纳米医学中最有前途的领域之一。特别是,纳米材料在细胞和组织内的识别和定位是理解其与生物成分相互作用的关键问题,即它们的细胞内化途径、细胞内靶标、治疗活性和可能的细胞毒性。在这里,我们通过为锌和氧化铁纳米粒子提供发光功能来展示多功能纳米粒子(NPs)的开发。我们描述了基于改良 Stöber 程序的简单合成方法,将荧光分子结合到氧化物 NPs 的表面上。这些程序涉及成功地将具有尺寸控制的无定形二氧化硅(SiO)壳涂覆在 NPs 上,该壳包含标准发色团,如荧光素、罗丹明 B 或罗丹明 B 异硫氰酸酯。具体而言,呈现了平均尺寸为 10nm 的球形 FeO NPs 和平均尺寸约为 130nm 的商业 ZnO NPs,它们分别涂覆有厚度约为 15nm 和 24nm 的无定形 SiO 壳。这些具有主要磁铁矿存在的磁性纳米粒子显示出可忽略的矫顽力。因此,相互作用(偶极子)非常弱,并且核心处于超顺磁状态。光谱测量证实了 SiO 壳内存在荧光分子,使这些混合 NPs 适合用于生物成像。因此,我们的涂层程序提高了 NP 在生理介质中的分散性,并允许使用共焦显微镜成像来识别和定位细胞内的 ZnO 和 FeO NPs,同时保持 NP 的荧光。我们证明了涂覆有发光 SiO 的 FeO 和 ZnO NPs 如何在 24 小时后被内化并积累在细胞质中。此外,SiO 壳提供了一个进一步功能化的平台,使设计靶向治疗策略成为可能。最后,我们研究了在不同生理环境中壳的降解,指出 SiO 涂层足够稳定,可以到达靶细胞并保持其原始结构。在暴露于不同介质 24 小时后,降解才开始发生。

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