Size effect of amphiphilic poly(γ-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo
Size effect of amphiphilic poly(γ-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo
复制标题
DOI：
10.1016/j.actbio.2013.06.010
复制
发表时间：
2013-11-01
影响因子：
9.7
通讯作者：
Akashi, Mitsuru
中科院分区：
文献类型：
--
作者：
Shima, Fumiaki;Uto, Tomofumi;Akashi, Mitsuru
我们制备了由两亲性聚（γ-谷氨酸）（γ-PGA）组成的尺寸可控的纳米颗粒（NPs）。在本研究中，采用40、100和200 nm的γ-PGA-接枝-L-苯丙氨酸乙酯（γ-PGA-Phe）纳米颗粒。纳米颗粒的大小显著影响抗原呈递细胞（APC）的摄取和活化行为。当40 nm的γ-PGA-Phe NPs在体外应用于这些细胞时，与100和200 nm的NPs相比，它们被高度活化，而细胞摄取是大小依赖性的。γ-PGA-Phe纳米粒的大小也显著影响其向淋巴结的迁移和树突状细胞（DCs）对纳米粒的体内摄取行为。与100和200 nm NP相比，40 nm γ-PGA-Phe NP更快速地迁移到淋巴结，并被更多数量的DC摄取。另一方面，当评估每个DC摄取的γ-PGA-Phe NP的量时，100和200 nm NP的量高于40 nm NP的量，这表明与较小的NP相比，较大的γ-PGA-Phe NP可以将大量抗原递送至单个DC。此外，当检查淋巴结中DC的成熟时，40 nm γ-PGA-Phe NP有效地刺激DC。这些结果表明，活化、APC的摄取行为、向淋巴结的迁移和DC成熟可以由γ-PGA-Phe NP的大小控制。(C)2013 Acts Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
We prepared size-regulated nanoparticles (NPs) composed of amphiphilic poly(gamma-glutamic acid) (gamma-PGA). In this study, 40, 100 and 200 nm gamma-PGA-graft-L-phenylalanine ethylester (gamma-PGA-Phe) NPs were employed. The size of NPs significantly influenced the uptake and activation behaviors of antigen-presenting cells (APCs). When 40 nm gamma-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 gamma-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 gamma-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 gamma-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 gamma-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 gamma-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 gamma-PGA-Phe NPs. (C) 2013 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.