The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation.

The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation.
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超顺磁性氧化铁纳米颗粒表面电荷对抗原交叉呈递的影响

DOI:
10.1186/s11671-017-1828-z
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发表时间:
2017-12
影响因子:
--
通讯作者:
Hu H
Hu H
中科院分区:
材料科学3区
文献类型:
--
作者:
Mou Y;Xing Y;Ren H;Cui Z;Zhang Y;Yu G;Urba WJ;Hu Q;Hu H

文献摘要

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超顺磁性氧化铁(SPIO)磁性纳米粒子(NPs)在生物医学、机械和信息等领域有着广泛的应用前景。在这里,我们探索了合成的SPIO NPs作为佐剂,通过增强抗原向抗原呈递细胞(APC)的细胞内递送来提高抗原交叉呈递能力。使用具有不同化学修饰和表面电荷的颗粒来研究抗原递送的作用机制。具体而言,制备了两种类型的磁性纳米颗粒,γ Fe 2 O3/APTS(3-氨丙基三甲氧基硅烷)纳米颗粒和γ Fe 2 O3/DMSA(meso-2,3-Dimercaptosuccinic acid)纳米颗粒,其具有相同的晶体结构、磁性和尺寸分布。然后,在不同的带电荷的抗原包被的NP之间比较通过树突状细胞(DC)的T细胞活化的促进。此外,自噬的激活,抗原的胞质递送,以及由蛋白酶体和溶酶体介导的抗原降解进行了测量。结果表明,带正电荷的γ Fe_2O_3/APTS NPs能增强DC的交叉呈递能力,而带负电荷的γ Fe_2O_3/DMSA NPs则不能。γ Fe 2 O3/APTS纳米粒诱导的交叉呈递能力的增加与细胞溶质抗原递送的增加相关。相反,γ Fe 2 O3/DMSA NPs与快速自噬相关。总体而言,我们的结果表明,由带正电的粒子诱导的细胞质中递送的抗原有利于抗原交叉递呈和T细胞活化。用不同的化学修饰的纳米颗粒表现出不同的生物学特性,并且在它们的佐剂潜力方面差异很大。因此,应仔细考虑纳米粒的多种不同作用,以设计有效且安全的佐剂。
Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared. Then, the promotion of T-cell activation via dendritic cells (DCs) was compared among different charged antigen coated NPs. Moreover, the activation of the autophagy, cytosolic delivery of the antigens, and antigen degradation mediated by the proteasome and lysosome were measured. Our results indicated that positive charged γFe2O3/APTS NPs, but not negative charged γFe2O3/DMSA NPs, enhanced the cross-presentation ability of DCs. Increased cross-presentation ability induced by γFe2O3/APTS NPs was associated with increased cytosolic antigen delivery. On the contrary, γFe2O3/DMSA NPs was associated with rapid autophagy. Overall, our results suggest that antigen delivered in cytoplasm induced by positive charged particles is beneficial for antigen cross-presentation and T-cell activation. NPs modified with different chemistries exhibit diverse biological properties and differ greatly in their adjuvant potentials. Thus, it should be carefully considered many different effects of NPs to design effective and safe adjuvants.