University of Texas Health Science Center, Department of NanoMedicine and Biomedical Engineering, 1825 Pressler Street, Suite 537, Houston, TX 77030, USA.
Nanoscale. 2010 Aug;2(8):1512-20. doi: 10.1039/c0nr00227e. Epub 2010 Jun 7.
Mesoporous silicon particles show great promise for use in drug delivery and imaging applications as carriers for second-stage nanoparticles and higher order particles or therapeutics. Modulation of particle geometry, surface chemistry, and porosity allows silicon particles to be optimized for specific applications such as vascular targeting and avoidance of biological barriers commonly found between the site of drug injection and the final destination. In this study, the intracellular trafficking of unloaded carrier silicon particles and carrier particles loaded with secondary iron oxide nanoparticles was investigated. Following cellular uptake, membrane-encapsulated silicon particles migrated to the perinuclear region of the cell by a microtubule-driven mechanism. Surface charge, shape (spherical and hemispherical) and size (1.6 and 3.2 microm) of the particle did not alter the rate of migration. Maturation of the phagosome was associated with an increase in acidity and acquisition of markers of late endosomes and lysosomes. Cellular uptake of iron oxide nanoparticle-loaded silicon particles resulted in sorting of the particles and trafficking to unique destinations. The silicon carriers remained localized in phagosomes, while the second stage iron oxide nanoparticles were sorted into multi-vesicular bodies that dissociated from the phagosome into novel membrane-bound compartments. Release of iron from the cells may represent exocytosis of iron oxide nanoparticle-loaded vesicles. These results reinforce the concept of multi-functional nanocarriers, in which different particles are able to perform specific tasks, in order to deliver single- or multi-component payloads to specific sub-cellular compartments.
介孔硅颗粒作为二级纳米颗粒和更高阶颗粒或治疗剂的载体,在药物传递和成像应用中具有很大的应用前景。通过调节颗粒的几何形状、表面化学性质和孔隙率,可以优化硅颗粒以适应特定的应用,如血管靶向和避免药物注射部位与最终目标之间常见的生物屏障。在这项研究中,研究了未负载载体硅颗粒和负载二级氧化铁纳米颗粒的载体颗粒的细胞内转运。在细胞摄取后,包膜硅颗粒通过微管驱动机制迁移到细胞的核周区域。颗粒的表面电荷、形状(球形和半球形)和尺寸(1.6 和 3.2 微米)不会改变迁移速度。吞噬体的成熟与酸度的增加以及晚期内体和溶酶体标志物的获得有关。氧化铁纳米颗粒负载硅颗粒的细胞摄取导致颗粒的分类和向独特的目的地转运。硅载体仍然定位于吞噬体中,而第二阶段的氧化铁纳米颗粒被分类到多泡体中,多泡体与吞噬体分离到新的膜结合隔室中。铁从细胞中的释放可能代表铁氧化物纳米颗粒负载囊泡的胞吐作用。这些结果强化了多功能纳米载体的概念,其中不同的颗粒能够执行特定的任务,以将单组分或多组分有效载荷递送到特定的亚细胞隔室。