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Endosomal/lysosomal location of organically modified silica nanoparticles following caveolae-mediated endocytosis

机译:小窝介导的内吞作用后有机修饰的二氧化硅纳米粒子的内体/溶酶体位置

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Organically modified silica (ORMOSIL) nanoparticles (NPs) are widely used in biomedicine. However, their cell uptake process has not yet been characterised in detail. Here, we investigated the mechanism underlying endocytosis and subcellular localisation of ORMOSIL NPs. Exposure to ORMOSIL NPs induced a decrease in cell viability and increase in lactate dehydrogenase release in a dose-dependent manner in A549 cells. Once internalised, ORMOSIL NPs were translocated from early endosomes to the lysosomes, where they accumulated. Furthermore, deficiency of autophagosomal/lysosomal fusion failed to block lysosomal localisation of ORMOSIL NPs, suggesting that autophagy was not involved in the final lysosomal accumulation of ORMOSIL NPs. Meanwhile, an inhibitor of caveolae-mediated endocytosis, rather than inhibitors of phagocytosis or clathrin-mediated endocytosis, succeeded in blocking ORMOSIL NP cell uptake, indicating the involvement of caveolae-mediated endocytosis. Together, these results provide a new understanding of the toxicity, and suggest better biomedical applications, of ORMOSIL NPs.
机译:有机改性的二氧化硅(ORMOSIL)纳米颗粒(NPs)被广泛用于生物医学。但是,它们的细胞摄取过程尚未详细表征。在这里,我们调查了内吞作用和ORMOSIL NPs的亚细胞定位的机制。在A549细胞中,暴露于ORMOSIL NPs以剂量依赖的方式诱导了细胞活力的降低和乳酸脱氢酶释放的增加。内化后,ORMOSIL NPs从早期的内体转移到溶酶体,并在那里积累。此外,自噬体/溶酶体融合的缺乏未能阻止ORMOSIL NP的溶酶体定位,这表明自噬不参与ORMOSIL NP的最终溶酶体积累。同时,小窝介导的内吞作用的抑制剂,而不是吞噬作用或网格蛋白介导的内吞作用的抑制剂,成功阻止了ORMOSIL NP细胞的摄取,表明小窝介导的内吞作用的参与。总之,这些结果为ORMOSIL NP的毒性提供了新的认识,并提出了更好的生物医学应用。

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