Yildirim Adem, Ozgur Erol, Bayindir Mehmet
UNAM-National Nanotechnology Research Center, Turkey.
J Mater Chem B. 2013 Apr 14;1(14):1909-1920. doi: 10.1039/c3tb20139b. Epub 2013 Feb 26.
Although numerous mesoporous silica nanoparticle (MSN) drug carriers and theranostic agents with various surface functionalities have been designed in the last decade, their biocompatibility remains a matter of intensive debate. Here, we systematically evaluated interactions of a series of MSNs possessing different surface functional groups (ionic, polar, neutral, and hydrophobic) with blood constituents, in terms of their hemolytic activity, thrombogenicity, and adsorption of blood proteins on their surfaces. Using a hemolysis assay we showed that surface functionalization can reduce or even completely prevent the hemolytic activity of bare MSNs. We investigated thrombogenicity of MSNs by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). We observed that none of the MSNs used in this study exhibit significant thrombogenic activity. Lastly, we examined non-specific protein adsorption on MSN surfaces using human serum albumin (HSA) and gamma globulins (γGs) and found that surface functionalization with ionic groups can greatly reduce protein adsorption. Demonstration of the surface functionalization having a crucial impact on blood compatibility might serve as a guideline for further investigation related to the design of mesoporous silica systems for biomedical applications, and shed light on research towards the ultimate goal of developing smart theranostic systems.
尽管在过去十年中已经设计出了许多具有各种表面功能的介孔二氧化硅纳米颗粒（MSN）药物载体和诊疗剂，但其生物相容性仍然是一个激烈争论的问题。在此，我们系统地评估了一系列具有不同表面官能团（离子型、极性、中性和疏水性）的MSN与血液成分之间的相互作用，包括它们的溶血活性、血栓形成性以及血液蛋白在其表面的吸附情况。通过溶血试验，我们表明表面功能化可以降低甚至完全防止裸MSN的溶血活性。我们通过测量凝血酶原时间（PT）和活化部分凝血活酶时间（aPTT）来研究MSN的血栓形成性。我们观察到本研究中使用的任何MSN均未表现出显著的血栓形成活性。最后，我们使用人血清白蛋白（HSA）和γ球蛋白（γG）检测了MSN表面的非特异性蛋白质吸附，发现离子基团的表面功能化可以大大减少蛋白质吸附。表面功能化对血液相容性具有关键影响的证明可能为进一步研究用于生物医学应用的介孔二氧化硅系统的设计提供指导，并为朝着开发智能诊疗系统这一最终目标的研究提供启示。
