Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
Small. 2022 Sep;18(38):e2203070. doi: 10.1002/smll.202203070. Epub 2022 Aug 19.
Nanoparticles are well established vectors for the delivery of a wide range of biomedically relevant cargoes. Numerous studies have investigated the impact of size, shape, charge, and surface functionality of nanoparticles on mammalian cellular uptake. Rigidity has been studied to a far lesser extent, and its effects are still unclear. Here, the importance of this property, and its interplay with particle size, is systematically explored using a library of core-shell spherical PEGylated nanoparticles synthesized by RAFT emulsion polymerization. Rigidity of these particles is controlled by altering the intrinsic glass transition temperature of their constituting polymers. Three polymeric core rigidities are tested: hard, medium, and soft using two particle sizes, 50 and 100 nm diameters. Cellular uptake studies indicate that softer particles are taken up faster and threefold more than harder nanoparticles with the larger 100 nm particles. In addition, the study indicates major differences in the cellular uptake pathway, with harder particles being internalized through clathrin- and caveolae-mediated endocytosis as well as macropinocytosis, while softer particles are taken up bycaveolae- and non-receptormediated endocytosis. However, 50 nm derivatives do not show any appreciable differences in uptake efficiency, suggesting that rigidity as a parameter in the biological regime may be size dependent.
纳米颗粒是广泛应用于生物医学相关领域的药物载体。已有大量研究探讨了纳米颗粒的尺寸、形状、电荷和表面功能对哺乳动物细胞摄取的影响。相比之下,纳米颗粒的刚性研究则相对较少,其影响也尚不明确。在这里,我们使用 RAFT 乳液聚合技术制备了一系列核壳结构的聚乙二醇化球形纳米颗粒,系统地研究了其刚性及其与粒径的相互作用。通过改变聚合物的固有玻璃化转变温度来控制这些颗粒的刚性。我们使用两种粒径(50nm 和 100nm),测试了三种聚合物核的刚性:硬、中、软。细胞摄取研究表明,与较大的 100nm 颗粒相比,较软的颗粒摄取速度更快,摄取量也增加了三倍。此外,该研究表明细胞摄取途径存在显著差异,较硬的颗粒通过网格蛋白和小窝蛋白介导的内吞作用以及巨胞饮作用被内化,而较软的颗粒则通过小窝蛋白和非受体介导的内吞作用被摄取。然而,50nm 的衍生物在摄取效率上没有表现出任何明显的差异,这表明在生物环境中,刚性作为一个参数可能与尺寸有关。