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Magnetic mesoporous silica nanoparticles for CpG delivery to enhance cytokine induction via toll-like receptor 9

机译:磁性介孔二氧化硅纳米颗粒,用于CpG递送,可通过通行费样受体9增强细胞因子的诱导作用

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摘要

We developed a potential cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) delivery system based on magnetic mesoporous silica (MMS) nanoparticles by binding of CpG ODN onto aminated MMS (MMS-NH2) nanoparticles to form CpG/MMS-NH2 complexes for toll-like receptor 9 (TLR9)-mediated induction of cytokines. Magnetization, serum stability, in vitro cytotoxicity, cellular uptake, and interleukin-6 (IL-6) induction of CpG/MMS-NH2 complexes were evaluated. The results showed that MMS nanoparticles exhibited superparamagnetic behavior with a saturation magnetization of 6.5 emu g(-1). Also, MMS-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and CpG/MMS-NH2 complexes enhanced the serum stability of CpG ODN and could be localized in the endolysosomes after endocytosis by cells. Importantly, CpG/MMS-NH2 complexes significantly enhanced the TLR9-mediated IL-6 induction compared to free CpG ODN. Therefore, CpG/MMS-NH2 complexes could exhibit magnetic targeted delivery and significantly enhance the TLR9-mediated cytokine induction for stimulating immune responses.
机译:我们通过将CpG ODN结合到胺化MMS(MMS-NH2)纳米颗粒上形成CpG / MMS-NH2复合物以形成收费的基础,我们开发了基于磁性介孔二氧化硅(MMS)纳米颗粒的潜在的胞嘧啶-磷酸-鸟苷寡聚脱氧核苷酸(CpG ODN)递送系统。像受体9(TLR9)介导的细胞因子诱导。评估了CpG / MMS-NH2复合物的磁化,血清稳定性,体外细胞毒性,细胞摄取和白介素6(IL-6)诱导。结果表明,MMS纳米粒子表现出超顺磁行为,饱和磁化强度为6.5 emu g(-1)。而且,MMS-NH2纳米颗粒对Raw 264.7细胞没有细胞毒性,CpG / MMS-NH2复合物增强了CpG ODN的血清稳定性,并且在细胞被细胞内吞后可以定位在溶酶体中。重要的是,与游离CpG ODN相比,CpG / MMS-NH2复合物显着增强了TLR9介导的IL-6诱导。因此,CpG / MMS-NH2复合物可以表现出磁性靶向递送,并显着增强TLR9介导的细胞因子诱导,以刺激免疫反应。

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