论文标题
纤维蛋白原纳米粒子生物缀合物与整合素的相互作用重构为人造膜
Interaction of fibrinogen-magnetic nanoparticle bioconjugates with integrin reconstituted into artificial membranes
论文作者
论文摘要
磁性纳米颗粒具有广泛的生物医学应用,包括细胞分离,诊断和治疗。一个关键问题很少探索:在注射后,工程纳米颗粒如何与血液成分相互作用?由于能够诱导免疫反应的能力,血液中生物缀合物的形成和随后的反应可能有毒。对基础过程的理解不仅与设计有效的纳米颗粒有关,还与针对有针对性的药物输送应用的安全纳米颗粒具有重大相关性。在这项研究中,我们报告了用柠檬酸盐,葡萄糖和聚乙二醇涂层功能化的岩岩纳米颗粒,以及它们与凝血蛋白纤维蛋白原的相互作用。此外,我们使用生物物理工具(例如,动态光散射,圆形二色性光谱和石英晶体微平衡)进行了研究,将磁性纳米粒子 - 纤维蛋白原生物偶联物与人工细胞膜作为血小板模型系统的相互作用。我们发现,纤维蛋白原电晕的形成为maghemite纳米颗粒提供了胶体稳定性。此外,纤维蛋白原与葡聚糖和柠檬酸盐涂层的NP相互作用的纤维蛋白原与含有脂质双层的整合素相互作用,尤其是在用二价离子处理后,而peg涂层则揭示了较小的相互作用。我们在蛋白质偶联的纳米颗粒和人造细胞膜的界面上进行的研究对于用于药物输送应用的安全纳米颗粒至关重要。
Magnetic nanoparticles have a broad spectrum of biomedical applications including cell separation, diagnostics and therapy. One key issue is little explored: how do the engineered nanoparticles interact with blood components after injection? The formation of bioconjugates in the bloodstream and subsequent reactions are potentially toxic due to the ability to induce an immune response. The understanding of the underlying processes is of major relevance to design not only efficient, but also safe nanoparticles for targeted drug delivery applications. In this study, we report on maghemite nanoparticles functionalized with citrate, dextran and polyethylene glycol coatings and their interaction with the clotting protein fibrinogen. Further, we investigate using biophysical tools (e.g. dynamic light scattering, circular dichroism spectroscopy and quartz crystal microbalance) the interaction of the magnetic nanoparticles-fibrinogen bioconjugates with artificial cell membranes as a model system for blood platelets. We found that fibrinogen corona formation provides colloidal stability to maghemite nanoparticles. In addition, bioconjugates of fibrinogen with dextran and citrate coated NPs interact with integrin containing lipid bilayer, especially upon treatment with divalent ions, whereas PEG-coating reveals minor interaction. Our study at the interface of protein-conjugated nanoparticles and artificial cell membranes is essential for engineering safe nanoparticles for drug delivery applications.