The hydrophobic effect of nanoparticles composed of amphiphilic poly(γ-glutamic acid) on the degradability of the encapsulated proteins
The hydrophobic effect of nanoparticles composed of amphiphilic poly(γ-glutamic acid) on the degradability of the encapsulated proteins
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两亲性聚γ-谷氨酸纳米粒子的疏水效应对包封蛋白质降解性的影响
DOI：
10.1039/c4bm00140k
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发表时间：
2014
影响因子：
6.6
通讯作者：
Mitsuru Akashi
中科院分区：
文献类型：
--
作者：
Fumiaki Shima;Takami Akagi;Mitsuru Akashi
为了开发安全有效的下一代疫苗载体，它们的物理化学性质（大小、形状、表面电荷和疏水/亲水平衡）对于控制它们与免疫细胞的相互作用（细胞摄取、负载抗原的细胞内降解性和细胞内定位）至关重要。近年来，载体的疏水性影响了细胞的摄取和免疫应答，表明疏水性是控制负载抗原和载体行为的重要因素之一。在这项研究中，我们研究了由两亲性聚（γ-谷氨酸）-接枝-苯丙氨酸乙酯（γ-PGA-Phe）组成的纳米颗粒（NPs）的疏水性与疏水侧链的不同接枝程度对包封抗原的细胞摄取、降解性及其在内体环境中的释放行为的影响。这些纳米粒子可以包裹蛋白质，并且纳米粒子的疏水性改变了包裹蛋白质的降解性。另一方面，纳米粒子的疏水性并不改变包封蛋白的释放行为。这些结果表明，包封的蛋白质的细胞内行为可以通过纳米颗粒的疏水性控制，并可能导致操纵抗原特异性免疫反应。
For the development of safe and effective next-generation vaccine carriers, their physicochemical properties (size, shape, surface charge, and hydrophobic/hydrophilic balance) are crucial to control their interactions (cellular uptake, intracellular degradability of the loaded antigen, and intracellular localization) with immune cells. Recently, the hydrophobicity of carriers affected the cellular uptake and immune response, which demonstrated that hydrophobicity is one of the most important factors to control the behaviors of the loaded antigens and carriers. In this study, we investigated the effect of the hydrophobicity of nanoparticles (NPs) composed of amphiphilic poly(γ-glutamic acid)-graft-phenylalanine ethyl ester (γ-PGA-Phe) with various grafting degrees of hydrophobic side chains on cellular uptake of the encapsulated antigens, their degradability, and their release behavior in the endosomal environment. These NPs could encapsulate proteins, and the degradability of the encapsulated proteins was changed by the hydrophobicity of NPs. On the other hand, the release behavior of the encapsulated proteins was not changed by the hydrophobicity of NPs. These results suggest that the intracellular behaviors of the encapsulated protein could be controlled by the hydrophobicity of NPs, and could result in the manipulation of the antigen-specific immune responses.