CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China and University of Chinese Academy of Sciences , Beijing 100190, China.
College of Science, Shenyang Agricultural University , Shenyang 110866, China.
ACS Nano. 2017 May 23;11(5):4606-4616. doi: 10.1021/acsnano.7b00200. Epub 2017 May 5.
When nanoparticles are exposed to a physiological environment, a "protein corona" is formed that greatly determines their biological fate. Adsorption of proteins could be influenced by chiral surfaces of nanoparticles; however, very few quantitative studies are available on the interaction of protein with the chiral surface of nanoparticles, and the underlying mechanism remains largely unresolved. We have developed a strategy to quantitatively analyze the adsorption and conformational features of transferrin on gold nanoparticles that are functionalized with d, l, and racemic penicillamine. We used a quartz microbalance platform to monitor the interaction of the adsorbed transferrin with transferrin receptors in HEK cell-derived liposomes. Results show that the chiral surface of nanoparticle determines the orientation and conformation of transferrin, which subsequently affects the interaction and recognition of transferrin with its receptor on the cellular membrane. Transferrin is widely used as a tumor-targeting ligand in cancer treatment and diagnosis since the transferrin receptor is overexpressed on the cell membrane of various types of cancer cells. Thus, the present results will help to expand the knowledge on biological identity of nanoparticles with chiral surfaces in a physiological environment and provide an insight into the rational design of therapeutic nanoparticles.
当纳米颗粒暴露于生理环境中时，会形成“蛋白质冠”，这极大地决定了它们的生物命运。蛋白质的吸附可能会受到纳米颗粒手性表面的影响；然而，关于蛋白质与纳米颗粒手性表面相互作用的定量研究非常少，其潜在机制在很大程度上仍未得到解决。我们开发了一种策略，可定量分析功能化的 d、l 和外消旋 penicillamine 的金纳米颗粒上转铁蛋白的吸附和构象特征。我们使用石英晶体微天平平台来监测吸附在转铁蛋白与 HEK 细胞衍生的脂质体中细胞膜上转铁蛋白受体的相互作用。结果表明，纳米颗粒的手性表面决定了转铁蛋白的取向和构象，进而影响转铁蛋白与其在细胞膜上的受体的相互作用和识别。由于转铁蛋白受体在各种类型的癌细胞的细胞膜上过表达，转铁蛋白被广泛用作癌症治疗和诊断中的肿瘤靶向配体。因此，目前的结果将有助于扩展在生理环境中具有手性表面的纳米颗粒的生物学特性的知识，并深入了解治疗性纳米颗粒的合理设计。
