PDF(Pubmed)
Abstract：
This work demonstrates that targeting ligand density on nanoparticles can affect interactions between the nanoconstructs and cell membrane receptors. We discovered that when the separation between covalently grafted DNA aptamers on gold nanostars was comparable to the distance between binding sites on a receptor dimer (matched density; MD), nanoconstructs exhibited a higher selectivity for binding to the dimeric form of the protein. Single-particle dynamics of MD nanoconstructs showed slower rotational rates and larger translational footprints on cancer cells expressing more dimeric forms of receptors (dimer+) compared with cells having more monomeric forms (dimer-). In contrast, nanoconstructs with either increased (nonmatched density; NDlow) or decreased ligand spacing (NDhigh) had minimal changes in dynamics on either dimer+ or dimer- cells. Real-time, single-particle analyses can reveal the importance of nanoconstruct ligand density for the selective targeting of membrane receptors in live cells.
摘要：
这项工作表明，纳米颗粒上的靶向配体密度可以影响纳米构建体和细胞膜受体之间的相互作用。我们发现，当金纳米星上共价接枝的DNA适体之间的分离与受体二聚体上的结合位点之间的距离相当时（匹配密度；MD），纳米构建体对结合二聚体形式的蛋白质表现出更高的选择性。与具有更多单体形式(二聚体-)的细胞相比,MD纳米构建体的单粒子动力学在表达更多二聚体形式的受体(二聚体+)的癌细胞上显示较慢的旋转速率和更大的翻译足迹。相比之下,具有增加的(非匹配密度;NDlow)或减少的配体间距(NDhigh)的纳米构建体在二聚体+或二聚体-细胞上的动力学变化最小。实时,单粒子分析可以揭示纳米构建体配体密度对活细胞中膜受体的选择性靶向的重要性。
