J Am Chem Soc. 2021 Mar 31;143(12):4550-4555. doi: 10.1021/jacs.1c00850. Epub 2021 Mar 18.
Nanoparticle carriers are effective drug delivery vehicles. Along with other design parameters including size, composition, and surface charge, particle shape strongly influences cellular uptake. How nanoparticle geometry affects targeted delivery under physiologically relevant conditions, however, is inconclusive. Here, we demonstrate that nanoconstruct core shape influences the dynamics of targeting ligand-receptor interactions on cancer cell membranes. By single-particle tracking of translational and rotational motion, we compared DNA aptamer AS1411 conjugated gold nanostars (AS1411-AuNS) and 50 nm gold spheres (AS1411-50NPs) on cells with and without targeted nucleolin membrane receptors. On nucleolin-expressing cells, AS1411-AuNS exhibited faster velocities under directed diffusion and translated over larger areas during restricted diffusion compared to AS1411-50NPs, despite their similar protein corona profiles. On nucleolin-inhibited cells, AS1411-AuNS showed faster rotation dynamics over smaller translational areas, while AS1411-50NPs did not display significant changes in translation. These differences in translational and rotational motions indicate that nanoparticle shape affects how targeting nanoconstructs bind to cell-membrane receptors.
纳米颗粒载体是有效的药物输送载体。除了其他设计参数（包括大小、组成和表面电荷）外，颗粒形状强烈影响细胞摄取。然而，纳米颗粒的几何形状如何在生理相关条件下影响靶向递送尚不清楚。在这里，我们证明了纳米结构核心形状会影响靶向配体-受体相互作用在癌细胞膜上的动力学。通过对平移和旋转运动的单粒子跟踪，我们比较了靶向核仁素细胞膜受体的 DNA 适体 AS1411 修饰的金纳米星（AS1411-AuNS）和 50nm 金纳米球（AS1411-50NPs）在有和没有靶向核仁素的细胞上的动力学。在核仁素表达的细胞上，与 AS1411-50NPs 相比，尽管它们具有相似的蛋白冠谱，但 AS1411-AuNS 在定向扩散下表现出更快的速度，并且在受限扩散期间翻译的面积更大。在核仁素抑制的细胞上，AS1411-AuNS 表现出更快的旋转动力学和更小的平移面积，而 AS1411-50NPs 在平移方面没有显示出显著变化。这些平移和旋转运动的差异表明，纳米颗粒的形状会影响靶向纳米结构与细胞膜受体的结合方式。
