Size-Dependent Mechanism of Intracellular Localization and Cytotoxicity of Mono-Disperse Spherical Mesoporous Nano- and Micron-Bioactive Glass Particles.
Size-Dependent Mechanism of Intracellular Localization and Cytotoxicity of Mono-Disperse Spherical Mesoporous Nano- and Micron-Bioactive Glass Particles.
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DOI：
10.1166/jbn.2016.2235
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发表时间：
2016-05
影响因子：
2.9
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Li Y;Hu Q;Miao G;Zhang Q;Yuan B;Zhu Y;Fu X;Chen X;Mao C
单分散球形介孔纳米和微米生物活性玻璃颗粒（NMBG）在骨组织工程中具有潜在的应用价值。然而，它们与成骨细胞的大小依赖性相互作用从未被研究过。在此，MC 3 T3-E1成骨细胞的增殖，形态，细胞骨架组织和凋亡的响应不同尺寸（从61到1085 nm）的NMBGs在不同浓度下进行了研究。一般来说，较小的NMBGs在较低剂量下显示较弱的细胞毒性相比，较大的颗粒和较高的剂量，从一个新的尺寸依赖性机制的细胞内定位的NMBGs观察电子和共聚焦显微镜。具体来说，NMBG穿过细胞的核周膜以启动内吞作用。一旦内化，发现NMBG的大小在确定其细胞内定位中起重要作用。当NMBG小于174 nm时，它们通过溶酶体途径转运并在溶酶体中被吞噬，导致在稍后的时间点几乎没有细胞毒性。相反，较大的NMBG（超过174 nm）在内吞作用后从溶酶体逃逸，并且定位在胞质内空泡内或随机地定位在细胞的胞质中。它们的溶酶体逃逸可能会破坏溶酶体，诱导细胞凋亡，从而产生更大的细胞毒性。
Mono-disperse spherical mesoporous nano- and micro- bioactive glass particles (NMBGs) can find potential use in bone tissue engineering. However, their size-dependent interaction with osteoblasts has never been studied. Herein, the proliferation, morphology, cytoskeleton organization and apoptosis of MC3T3-E1 osteoblasts are studied in response to the NMBGs with varying sizes (from 61 to 1085 nm) at different concentrations. Generally, smaller NMBGs at a lower dose show weaker cytotoxicity compared to the larger particles and higher doses, arising from a novel size-dependent mechanism of intracellular localization of NMBGs observed by electron and confocal microscopy. Specifically, NMBGs pass through perinuclear membrane of the cells to initiate endocytosis. Once internalized, the sizes of NMBGs are found to play a significant role in determining their intracellular localization. When the NMBGs are smaller than 174 nm, they are transported via the lysosomal pathway and phagocytized in lysosomes, resulting in little cytotoxicity at later time points. On the contrary, larger NMBGs (over 174 nm) escape from the lysosomes after endocytosis, and are localized inside the intra-cytoplasmic vacuoles or randomly in the cytoplasm of cells. Their lysosomal escape may damage the lysosomes, inducing cell apoptosis and thus the greater cytotoxicity.