Glioblastoma (GBM) is an aggressive disease with currently no satisfying treatment option available. GBM cells with stem cell properties are thought to be responsible for the initiation and propagation of the disease, as well as main contributors to the emergence of therapy resistance. In this work, we developed a novel method to synthesize fluorescent gold nanoparticles as potential drug and gene delivery systems for GBM therapy, able to penetrate three-dimensional stem cell selected patient-derived GBM neurosphere systems in vitro. By using polyethylene imine (PEI) as a stabilizer and reducing agent, as well as fluorescein isothiocyanate (FITC) as a fluorescent marker, our fully in-house developed fluorescent gold nanoparticles (AuPEI-FITC NPs) with core sizes between 3 and 6 nm were obtained via a fast microwave-assisted reaction. Cytotoxicity, adsorption and internalization of AuPEI-FITC NPs into the cell lines JHH520, 407 and GBM1 were investigated using the cellular growth assay and fluorescence-activated cell sorting (FACS) analysis. AuPEI-FITC NPs showed no apparent cytotoxicity and an uptake in cells of up to ~80%. A differentiation between surface-bound and internalized AuPEI-FITC NPs was possible by quenching extracellular signals. This resulted in a maximal internalization degree of 61%, which depends highly on the synthesis method of the nanoparticles and the cell type tested. The best internalization was found for AuPEI-FITC1 which was prepared in a one pot reaction from KAuCl4, PEI and FITC. Thus, appropriately synthesized AuPEI-FITC NPs show great potential as vehicles to transport DNA or drugs in GBM cells.

中文翻译：

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合成方法对荧光金纳米颗粒内化成胶质母细胞瘤干样细胞的影响。

胶质母细胞瘤（GBM）是一种侵袭性疾病，目前尚无令人满意的治疗选择。具有干细胞特性的GBM细胞被认为是该疾病的发生和传播的原因，也是导致治疗耐药性的主要因素。在这项工作中，我们开发了一种新颖的方法来合成荧光金纳米粒子，作为GBM治疗的潜在药物和基因递送系统，能够在体外穿透三维干细胞选择的患者来源的GBM神经球系统。通过使用聚乙烯亚胺（PEI）作为稳定剂和还原剂，以及异硫氰酸荧光素（FITC）作为荧光标记，我们完全自主研发的荧光金纳米颗粒（AuPEI-FITC NPs）的核心尺寸为3至6 nm通过快速微波辅助反应获得。细胞毒性 使用细胞生长测定法和荧光激活细胞分选（FACS）分析了AuPEI-FITC NP在JHH520、407和GBM1细胞系中的吸附和内在化。AuPEI-FITC NPs没有表现出明显的细胞毒性，细胞吸收率高达〜80％。通过淬灭细胞外信号，可以区分表面结合和内在化的AuPEI-FITC NP。这导致最大内部化程度为61％，这在很大程度上取决于纳米颗粒的合成方法和所测试的细胞类型。发现最佳的内在化是AuPEI-FITC1，它是由KAuCl4，PEI和FITC一锅反应制得的。因此，适当合成的AuPEI-FITC NPs具有巨大的潜力，可以作为在GBM细胞中转运DNA或药物的媒介。