The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Chemistry. 2018 Jun 18;24(34):8513-8518. doi: 10.1002/chem.201800525. Epub 2018 May 16.
A quantitative understanding of the sub-cellular distributions of nanospheres taken up by cells is of key importance to the development of effective nanomedicine. With gold nanospheres as a model system, here we demonstrate, for the first time, how to quantify the numbers of nanospheres bound to plasma membrane, accumulated in cytosol, and entrapped in endo-lysosomes, respectively, through stepwise, site-selective etching. Our results indicate that the chance for nanospheres to escape from endo-lysosomes is insensitive to the presence of targeting ligand although ligand-receptor binding has been documented as a critical factor in triggering internalization. Furthermore, the presence of serum proteins is shown to facilitate the binding of nanospheres to plasma membrane lacking the specific receptor. Collectively, these findings confirm the potential of stepwise etching in quantitatively analyzing the sub-cellular distributions of nanospheres taken up by cells in an effort to optimize the therapeutic effect.
定量了解细胞内纳米球的亚细胞分布对于开发有效的纳米医学至关重要。本文以金纳米球为模型系统，首次展示了如何通过逐步、选择性刻蚀，分别定量测定与质膜结合、在胞质中积累和内吞体中包裹的纳米球的数量。我们的结果表明，尽管已有文献报道配体-受体结合是触发内吞作用的关键因素，但纳米球从内吞体逃逸的机会与靶向配体的存在无关。此外，还表明血清蛋白的存在有助于纳米球与缺乏特异性受体的质膜结合。总的来说，这些发现证实了分步刻蚀在定量分析细胞摄取的纳米球亚细胞分布方面的潜力，有助于优化治疗效果。
