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Lactosylated N-Alkyl polyethylenimine coated iron oxide nanoparticles induced autophagy in mouse dendritic cells

机译:乳糖化的N-烷基聚乙烯亚胺包覆的氧化铁纳米颗粒诱导小鼠树突状细胞的自噬

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Dendritic cell (DC)-based vaccines have shown promising therapeutic results in cancer and some immune disorders. It is critical to track in vivo migration behaviours of DCs and monitor the whole process dynamically and non-invasively. Superparamagnetic iron oxide (SPIO) nanoparticles are chosen for DC labelling under magnetic resonance imaging (MRI) because of their proven biosafety as contrast agents. However, when used for cell labelling, sensitive biological indicators such as cell autophagy may be helpful to better understand the process and improve the probe design. Here, lactosylated N-Alkyl polyethylenimine coated SPIO nanoparticles are used for DC labelling. This probe shows satisfactory cell labelling efficiency and low cytotoxicity. In this study, autophagy was used as a key factor to understand how DCs react to nanoparticles after labelling. Our results demonstrate that the nanoparticles can induce protective autophagy in DCs, as inhibition of the autophagy flux could lead to cell death. Meanwhile, the nanoparticles induced autophagy could promote DC maturation which is an essential process for its migration and antigen presentation. Autophagy induced DC maturation is known to enhance the vaccine functions of DCs, therefore, our results suggest that beyond the MRI tracking ability, this probe might enhance therapeutic immune activation as well.
机译:基于树突细胞(DC)的疫苗在癌症和某些免疫疾病中显示出令人鼓舞的治疗效果。跟踪DC的体内迁移行为并动态且无创地监控整个过程至关重要。选择超顺磁性氧化铁(SPIO)纳米颗粒进行磁共振成像(MRI)进行DC标记,是因为它们作为造影剂已被证明具有生物安全性。但是,当用于细胞标记时,敏感的生物指示剂(例如细胞自噬)可能有助于更好地了解过程并改善探针设计。在这里,乳糖基化的N-烷基聚乙烯亚胺涂层的SPIO纳米颗粒用于DC标记。该探针显示令人满意的细胞标记效率和低细胞毒性。在这项研究中,自噬被用作了解标记后DC对纳米颗粒反应的关键因素。我们的结果表明,纳米颗粒可以诱导DC中的保护性自噬,因为抑制自噬通量可能导致细胞死亡。同时,纳米粒子诱导的自噬可以促进DC成熟,这是其迁移和抗原呈递的必不可少的过程。自噬诱导的DC成熟可以增强DC的疫苗功能,因此,我们的结果表明,除了MRI追踪能力之外,该探针还可能增强治疗性免疫激活。

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