文章：

人肺间充质干细胞作为放射增敏金属纳米颗粒载体的潜力：一项体外研究

The Potential of Human Pulmonary Mesenchymal Stem Cells as Vectors for Radiosensitizing Metallic Nanoparticles: An In Vitro Study

原文发布日期：23 September 2024

DOI: 10.3390/cancers16183239

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Metallic nanoparticles (NPs) exhibit interesting radiosensitizing effects, and finding a way to accurately deliver them appears to be crucial. Due to their tumor tropism, mesenchymal stem cells (MSCs) represent a strategic approach. Therefore, we aimed to evaluate the impact of core–shell Fe3O4@Au NPs on the functionality of human pulmonary MSCs (HPMSCs). Methods/Results: The results showed that 100 µg/mL Fe3O4@Au NPs, accumulated in HPMSCs (revealed by Prussian blue staining), did not alter cell viability as assessed by cell counting, MTT, and LDH assays. However,caspase 9andBcl2gene expression, evaluated by RT-qPCR, was regulated 72 h after exposure to the NPs. Moreover, the NPs also decreased proinflammatory cytokine/chemokine secretions, except for CXCL8 (ELISA). These modulations were associated with the downregulation ofAMPKgene expression at 24 h. In contrast, the NPs did not modulateVEGF,PI3K, orPDGFgene expression. Nevertheless, a decrease in VEGF secretion was observed after 24 h of exposure to the NPs. Interestingly, the Fe3O4@Au NPs did not modulateNrf2gene expression, but they did regulate the expression of the genes encoding Nox4 and HMOX-1. Additionally, the NPs increased ROS production, suggesting a redox imbalance. Conclusions: Finally, the Fe3O4@Au NPs did not affect the HPMSCs’ viability or proangiogenic/tumorigenic markers. These findings are encouraging for investigating the effects of Fe3O4@Au NPs delivered by HPMSCs to tumor sites in combination with radiation.

摘要翻译： 

背景/目的：金属纳米粒子（NPs）展现出引人注目的放射增敏效应，因此寻找一种精确递送这些纳米粒子的方法显得至关重要。间充质干细胞（MSCs）因其肿瘤趋向性，代表了一种策略性递送途径。本研究旨在评估核壳结构Fe3O4@Au NPs对人肺间充质干细胞（HPMSCs）功能的影响。方法/结果：结果显示，通过普鲁士蓝染色证实，在HPMSCs内累积的100 µg/mL Fe3O4@Au NPs，经细胞计数、MTT和LDH检测评估，未改变细胞活力。然而，通过RT-qPCR评估发现，暴露于纳米粒子72小时后，caspase 9和Bcl2基因表达受到调控。此外，除CXCL8外（ELISA检测），纳米粒子还降低了促炎细胞因子/趋化因子的分泌（ELISA检测）。这些调控与暴露24小时后AMPK基因表达的下调相关。相比之下，纳米粒子未对VEGF、PI3K或PDGF基因表达产生调控作用。然而，暴露于纳米粒子24小时后，观察到VEGF分泌减少。有趣的是，Fe3O4@Au NPs未调控Nrf2基因表达，但确实调控了编码Nox4和HMOX-1的基因表达。此外，纳米粒子增加了活性氧（ROS）的产生，提示存在氧化还原失衡。结论：综上所述，Fe3O4@Au NPs不影响HPMSCs的活力或促血管生成/致瘤性标志物。这些发现为研究HPMSCs递送Fe3O4@Au NPs至肿瘤部位联合放疗的效果提供了鼓舞人心的依据。

原文链接：

The Potential of Human Pulmonary Mesenchymal Stem Cells as Vectors for Radiosensitizing Metallic Nanoparticles: An In Vitro Study