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Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity

机译:静脉给药的金纳米颗粒取决于粒径,穿过血视网膜屏障,不会引起视网膜毒性

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摘要

The retina maintains homeostasis through the blood-retinal barrier (BRB). Although it is ideal to deliver the drug to the retina via systemic administration, it is still challenging due to the BRB strictly regulating permeation from blood to the retina. Herein, we demonstrated that intravenously administered gold nanoparticles could pass through the BRB and are distributed in all retinal layers without cytotoxicity. After intravenous injection of gold nanoparticles into C57BL/6 mice, 100 nm nanoparticles were not detected in the retina whereas 20 nm nanoparticles passed through the BRB and were distributed in all retinal layers. 20 nm nanoparticles in the retina were observed in neurons (75 +/- 5%), endothelial cells (17 +/- 6%) and peri-endothelial glial cells (8 +/- 3%), where nanoparticles were bound on the membrane. In the retina, cells containing nanoparticles did not show any structural abnormality and increase of cell death compared to cells without nanoparticles. Gold nanoparticles never affected the viability of retinal endothelial cells, astrocytes and retinoblastoma cells. Furthermore, gold nanoparticles never led to any change in expression of representative biological molecules including zonula occludens-1 and glut-1 in retinal endothelial cells, neurofilaments in differentiated retinoblastoma cells and glial fibrillary acidic protein in astrocytes. Therefore, our data suggests that small gold nanoparticles (20 nm) could be an alternative for drug delivery across the BRB, which could be safely applied in vivo.
机译:视网膜通过血视网膜屏障(BRB)维持体内平衡。尽管理想的是通过全身给药将药物输送到视网膜,但由于BRB严格调节从血液到视网膜的渗透,因此仍然具有挑战性。在本文中,我们证明了静脉内施用的金纳米颗粒可以通过BRB,并分布在所有视网膜层中而没有细胞毒性。在将金纳米颗粒静脉注射到C57BL / 6小鼠中后,在视网膜中未检测到100 nm纳米颗粒,而20 nm纳米颗粒穿过BRB并分布在所有视网膜层中。在神经元(75 +/- 5%),内皮细胞(17 +/- 6%)和内皮周围神经胶质细胞(8 +/- 3%)中观察到了视网膜中的20 nm纳米颗粒,其中纳米颗粒结合在膜。在视网膜中,与没有纳米颗粒的细胞相比,含有纳米颗粒的细胞没有显示任何结构异常和细胞死亡的增加。金纳米颗粒从未影响视网膜内皮细胞,星形胶质细胞和成视网膜细胞瘤细胞的生存能力。此外,金纳米颗粒从未导致视网膜内皮细胞中的小带闭合蛋白-1和glut-1,分化的成视网膜细胞瘤细胞中的神经丝以及星形胶质细胞中的胶质纤维酸性蛋白的代表性生物分子的表达没有任何变化。因此,我们的数据表明,小的金纳米颗粒(20 nm)可以作为跨BRB的药物输送的替代方法,可以安全地应用于体内。

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