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金纳米粒子靶向递送顺铂:通过 CE-ICP-MS/MS 考察纳米载体表面修饰类型对药物结合效率的影响。

Targeted Delivery of Cisplatin by Gold Nanoparticles: The Influence of Nanocarrier Surface Modification Type on the Efficiency of Drug Binding Examined by CE-ICP-MS/MS.

机构信息

Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland.

Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland.

出版信息

Int J Mol Sci. 2022 Feb 19;23(4):2324. doi: 10.3390/ijms23042324.

Abstract

Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle-cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold-drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface's processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH, and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability.

摘要

球形金纳米粒子(GNPs)因其在生物医学应用方面的独特性质而受到广泛研究,作为药物靶向传递系统(DTDS)中的纳米载体备受关注。表面功能化的可能性,特别是在延长在血液中的半衰期和增强细胞摄取方面,提供了克服由于其非选择性运输而导致严重副作用的流行抗癌药物(如顺铂)的局限性的机会。在此,我们研究了金纳米粒子-顺铂系统的形成(关于反应动力学和平衡),证明了形成效率和稳定性强烈依赖于纳米粒子的表面功能化。在这项研究中,首次使用毛细管电泳与电感耦合等离子体质谱串联质谱(CE-ICP-MS/MS)监测金-药物纳米复合物的形成。研究包括优化 CE 分离条件和使用开发的 CE-ICP-MS/MS 方法确定反应动力学。为了表征纳米载体并描绘表面过程引起的其物理化学性质的变化,还通过动态光散射(DLS)测量进行了额外的水动力粒径和 ζ-电位测量。对三种类型的功能化 GNPs(GNP-PEG-COOH、GNP-PEG-OCH 和 GNP-PEG-生物素)的检查区分了药物结合效率和纳米复合物稳定性的重要差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/8874575/4bbef60424f8/ijms-23-02324-g001.jpg

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