The Size and Surface Modification of Amorphous Silica Particles Affect the Biological Processes in Murine Macrophages
The Size and Surface Modification of Amorphous Silica Particles Affect the Biological Processes in Murine Macrophages
复制标题
无定形二氧化硅颗粒的尺寸和表面修饰影响小鼠巨噬细胞的生物过程
DOI：
10.1166/jnn.2017.12811
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发表时间：
2017-02-01
影响因子：
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通讯作者：
Fan, Xiaohui
中科院分区：
文献类型：
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作者：
Lu, Xiaoyan;Jin, Tingting;Fan, Xiaohui
无定形二氧化硅颗粒（SP）的物理化学性质对生物系统的影响是研究最多的，特别是粒径和表面改性。然而，关于多种理化性质如何综合影响SP对生物系统的响应的研究非常有限。本研究的目的是确定SP在细胞内的大小和表面修饰的综合效应，包括细胞摄取的机制及其与生物过程的可能相互作用。荧光染料共价结合SP与各种直径（30，70，和300 nm）和表面改性（平原，氨基（-NH 2），和羧基（-COOH）基团）。这些荧光SP的大小和zeta电位在悬浮液中进行了表征。观察SP对巨噬细胞（RAW264.7细胞）生物学反应的影响，包括细胞毒性、氧化应激、对细胞周期的影响和诱导凋亡。结果表明，所有SP均能诱导巨噬细胞产生剂量依赖性的细胞毒作用，其机制可能与诱导氧化应激，引起巨噬细胞凋亡和坏死有关。此外，表面修饰似乎是产生活性氧簇和影响细胞周期过程的更关键因素。只有平坦表面的SP均诱导cyclin D1和CDK 4蛋白表达减少，最终导致G1期阻滞。三种70 nm SP（SP 70）的内化颗粒总量和细胞器定位几乎相同，但羧基修饰的SP 70内化速度快于普通表面和氨基修饰的SP 70。此外，这三个不同的表面SP 70的细胞摄取是能量依赖性的，和肌动蛋白丝可能参与平面SP 70的内化。综上所述，本研究提供了关于SP在细胞内的多种理化性质依赖性效应的进一步见解，并将有助于设计安全有效的SP形式。
The effects of individual physicochemical property of amorphous silica particles (SP) on biological systems have been most frequently studied, especially the size and surface modification. However, the studies on how multiple physicochemical properties integrally influence the responses of SP on biological systems are very limited. The motivation of this study was to determine the combined effects of size and surface modification of SP within cells, including the mechanisms of cellular uptake and their possible interactions with biological processes. Fluorescent dye covalently bound SP with various diameters (30, 70, and 300 nm) and surface modifications (plain, amino(-NH2), and carboxyl (-COOH) groups) were used. The size and zeta potential of these fluorescent SP in suspensions were characterized. The effects of SP on biological responses in macrophages (RAW264.7 cells), including cytotoxicity, oxidative stress, impact on cell cycle, and induction of apoptosis, were evaluated. We found all the SP induced dose-dependent cytotoxicity, and the mechanism is referred to induce oxidative stress and cause apoptosis and necrosis in macrophages. Moreover, surface modification seems to be a more critical factor in generating reactive oxygen species and affecting the cell cycle process. Only the plain surface SP all induced a decrease in the expression of cyclin D1 and CDK4 proteins, ultimately leading to G1 phase arrest. The total amount of internalized particles and organelles localization were almost the same among the three types of 70 nm SP (SP70), but carboxyl-modified SP70 internalized faster than plain surface and amino-modified SP70. Additionally, the cellular uptake of these three different surfaces SP70 was energy-dependent, and actin filaments may be involved in the internalization of plain surface SP70. Taken together, this study provided the further insights regarding the multiple physicochemical properties-dependent effects of SP within cells and will assist in the design of safe and effective forms of SP.