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一步合成含羧基钌配合物的聚合物核壳颗粒:一种用于生物医学应用的潜在工具。

One-step synthesis of polymer core-shell particles with a carboxylated ruthenium complex: a potential tool for biomedical applications.

作者信息

Linares Elisângela M, Formiga André, Kubota Lauro T, Galembeck Fernando, Thalhammer Stefan

机构信息

Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.

出版信息

J Mater Chem B. 2013 May 7;1(17):2236-2244. doi: 10.1039/c3tb00316g. Epub 2013 Feb 25.

DOI:10.1039/c3tb00316g
PMID:32260876
Abstract

Luminescent core-shell particles are structures widely applied to biomedical purposes with the potential of combining multiple features within one single particle. The development of particles that are easily synthesised and tunable for each application, combining biocompatibility, easy bioconjugation and a high detection signal as a label, is highly desired. In this work, we describe a one-step synthesis of poly[styrene-co-(2-hydroxyethyl methacrylate)], PSHEMA, core-shell particles containing [Ru(4,4'-dicarboxilate-2,2'-bpy)] luminescent complexes. These particles show monodispersity, biocompatibility, easy functionalization and dye incorporation to focus on bioapplications, such as cell-tracking and diagnostics. The monomers assemble during the polymerization and produce core-shell structures with hydrophilic-hydrophobic character. This allows the concentration of hydrophilic ruthenium complexes onto the shell and incorporation of hydrophobic molecules (e.g. diphenylanthracene) due to the hydrophobic character of styrene. The incorporation of the Ru complex resulted in higher photostability compared to the free dye. Furthermore, carboxylic groups on the particle surface originated from carboxylated ligands of Ru complexes were used to immobilize biomolecules. The particles were successfully used as a diagnostic label for dengue fever (DF) infection. Using the complexes in the immunospot assay the test provided a detection limit (DL) of 187 ng mL for the viral non-structural glycoprotein NS1. The particles showed a considerable decrease in the DL and allowed the diagnosis of the infection 24 hours earlier compared to common available assays based on gold nanoparticles. In addition, the particles were tested with an adherent grown fibroblast cell line and showed potential biocompatibility.

摘要

发光核壳颗粒是广泛应用于生物医学领域的结构,具有在单个颗粒中结合多种特性的潜力。人们迫切需要开发出易于合成且可针对每种应用进行调节的颗粒,这些颗粒要兼具生物相容性、易于生物共轭以及作为标记的高检测信号。在这项工作中,我们描述了一种一步合成聚[苯乙烯 - 共 -(甲基丙烯酸2 - 羟乙酯)](PSHEMA)核壳颗粒的方法,该颗粒含有[Ru(4,4'-二羧酸 - 2,2'-联吡啶)]发光配合物。这些颗粒具有单分散性、生物相容性、易于功能化以及可掺入染料等特点,适用于细胞追踪和诊断等生物应用。单体在聚合过程中组装形成具有亲水 - 疏水特性的核壳结构。这使得亲水性钌配合物集中在壳层上,并且由于苯乙烯的疏水特性,可以掺入疏水分子(如二苯基蒽)。与游离染料相比,Ru配合物的掺入导致更高的光稳定性。此外,颗粒表面源自Ru配合物羧化配体的羧基用于固定生物分子。这些颗粒成功地用作登革热(DF)感染的诊断标记。在免疫斑点试验中使用这些配合物,该测试对病毒非结构糖蛋白NS1的检测限(DL)为187 ng/mL。与基于金纳米颗粒的现有常见检测方法相比,这些颗粒的检测限显著降低,并且能够提前24小时诊断感染。此外,这些颗粒在贴壁生长的成纤维细胞系上进行了测试,显示出潜在的生物相容性。

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