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人肺间充质干细胞作为金属纳米颗粒放射增敏载体的潜力:一项体外研究

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

作者信息

Arcambal Angélique, Septembre-Malaterre Axelle, Pesnel Sabrina, Morel Anne-Laure, Gasque Philippe, Begue Mickael, Slama Youssef

机构信息

Laboratoire Interdisciplinaire de Recherche en Santé (LIRS), RunResearch, Sainte-Clotilde Clinic, 127 Route de Bois de Nèfles, 97400 Saint-Denis, Reunion Island, France.

Unité de Recherche Etudes Pharmaco-Immunologiques (EPI), University of La Réunion, CHU of La Réunion, Felix Guyon Site, Allée des Topazes, SC11021, 97400 Saint-Denis, Reunion Island, France.

出版信息

Cancers (Basel). 2024 Sep 23;16(18):3239. doi: 10.3390/cancers16183239.

Abstract

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 FeO@Au NPs on the functionality of human pulmonary MSCs (HPMSCs).

METHODS/RESULTS: The results showed that 100 µg/mL FeO@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, and gene 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 of gene expression at 24 h. In contrast, the NPs did not modulate , , or gene expression. Nevertheless, a decrease in VEGF secretion was observed after 24 h of exposure to the NPs. Interestingly, the FeO@Au NPs did not modulate gene 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 FeO@Au NPs did not affect the HPMSCs' viability or proangiogenic/tumorigenic markers. These findings are encouraging for investigating the effects of FeO@Au NPs delivered by HPMSCs to tumor sites in combination with radiation.

摘要

背景/目的:金属纳米颗粒(NPs)具有有趣的放射增敏作用,找到准确递送它们的方法似乎至关重要。由于其肿瘤嗜性,间充质干细胞(MSCs)是一种具有战略意义的方法。因此,我们旨在评估核壳型FeO@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,普鲁士蓝染色显示在HPMSCs中积累的100μg/mL FeO@Au NPs,通过细胞计数、MTT和LDH测定评估,并未改变细胞活力。然而,通过RT-qPCR评估,暴露于NPs 72小时后, 和 基因表达受到调控。此外,除CXCL8外(ELISA法),NPs还降低了促炎细胞因子/趋化因子的分泌。这些调节与24小时时 基因表达的下调有关。相反,NPs未调节 、 或 基因表达。然而,暴露于NPs 24小时后观察到VEGF分泌减少。有趣的是,FeO@Au NPs未调节 基因表达,但它们确实调节了编码Nox4和HMOX-1的基因的表达。此外,NPs增加了ROS的产生,表明存在氧化还原失衡。

结论

最后,FeO@Au NPs不影响HPMSCs的活力或促血管生成/致瘤标记物。这些发现对于研究HPMSCs递送的FeO@Au NPs与辐射联合作用于肿瘤部位的效果具有鼓舞作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d192/11430180/7462c931ea20/cancers-16-03239-g001.jpg

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