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Size effect of amphiphilic poly(γ-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo

机译:两亲性聚(γ-谷氨酸)纳米粒子对体内树突状细胞摄取和成熟的大小影响

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We prepared size-regulated nanoparticles (NPs) composed of amphiphilic poly(γ-glutamic acid) (γ-PGA). In this study, 40, 100 and 200 nm γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) NPs were employed. The size of NPs significantly influenced the uptake and activation behaviors of antigen-presenting cells (APCs). When 40 nm γ-PGA-Phe NPs were applied to these cells in vitro, they were highly activated compared with 100 and 200 nm NPs, while cellular uptake was size dependent. The size of the γ-PGA-Phe NPs also significantly affected their migration to the lymph nodes and uptake behavior of NPs by dendritic cells (DCs) in vivo. The 40 nm γ-PGA-Phe NPs migrated more rapidly to the lymph nodes and were taken up by a greater number of DCs compared with 100 and 200 nm NPs. On the other hand, when the amount of γ-PGA-Phe NPs taken up per DC was evaluated, it was higher for 100 and 200 nm NPs than for 40 nm NPs, which suggests that the larger γ-PGA-Phe NPs can deliver a large amount of antigen to a single DC compared with smaller NPs. Furthermore, when examined the maturation of DCs in lymph nodes, 40 nm γ-PGA-Phe NPs efficiently stimulated DCs. These results suggest that the activation, uptake behavior by APCs, migration to lymph nodes, and DC maturation can be controlled by the size of γ-PGA-Phe NPs.
机译:我们准备了由两亲性聚(γ-谷氨酸)(γ-PGA)组成的尺寸可调节的纳米颗粒(NPs)。在这项研究中,使用了40、100和200 nm的γ-PGA-接枝-1-苯丙氨酸乙酯(γ-PGA-Phe)NP。 NP的大小显着影响抗原呈递细胞(APC)的摄取和激活行为。当在体外将40 nmγ-PGA-PheNP应用于这些细胞时,与100和200 nm NP相比,它们被高度激活,而细胞摄取则取决于大小。 γ-PGA-PheNP的大小也显着影响其向淋巴结的迁移以及体内树突状细胞(DC)对NP的吸收行为。与100和200 nm NP相比,40 nmγ-PGA-PheNP迁移到淋巴结的速度更快,并被更多的DC吸收。另一方面,当评估每个DC吸收的γ-PGA-PheNP数量时,其100和200 nm NP的数量要高于40 nm NP,这表明较大的γ-PGA-PheNP可以递送。与较小的NP相比,单个DC需要大量抗原。此外,当检查淋巴结中DC的成熟时,40 nmγ-PGA-PheNP可以有效刺激DC。这些结果表明,γ-PGA-PheNP的大小可以控制APC的激活,摄取行为,向淋巴结的迁移和DC成熟。

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