Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
PLoS One. 2012;7(7):e40775. doi: 10.1371/journal.pone.0040775. Epub 2012 Jul 10.
The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different intrinsic surface properties.
由于其较大的表面积，外围肺部是纳米粒子进入人体的潜在入口。纳米粒子可以沉积在肺部的肺泡区域，这对于肺部药物输送策略很重要，并且对于毒理学考虑也同样重要。因此，详细了解纳米粒子与肺部这个最大和最敏感部分的结构之间的相互作用对于纳米医学和纳米毒理学都很重要。令人惊讶的是，对于肺泡中纳米粒子沉积后发生的生物-纳米相互作用，我们仍然知之甚少。在这项研究中，我们使用流式细胞术和共聚焦显微镜比较了表面活性剂相关蛋白 A (SP-A) 和 D (SP-D) 对具有不同亲水性（淀粉）或疏水性（磷脂酰胆碱）表面修饰的磁铁矿纳米颗粒（mNP）清除作用的影响，肺泡巨噬细胞（AM）细胞系（MH-S）。与原始纳米颗粒相比，这两种蛋白质都增强了 AM 对 mNP 的摄取；对于亲水性 ST-mNP，这种作用在 SP-D 中最强，而对于疏水性 PL-mNP，在 SP-A 中最为明显。使用凝胶电泳和动态光散射方法，我们能够证明观察到的细胞效应与蛋白质吸附和蛋白质介导的胶体稳定性干扰有关。接下来，我们研究了各种表面活性剂脂质对 AM 摄取纳米颗粒的影响，因为脂质是主要的表面活性剂成分。合成表面活性剂脂质和分离的天然表面活性剂制剂分别显著调节了 SP-A 和 SP-D 所产生的作用，导致亲水性和疏水性纳米颗粒的巨噬细胞相互作用水平相当。我们的发现表明，由于表面活性剂脂质和蛋白质的相互作用，AM 对纳米颗粒的清除基本相同，而与不同的固有表面特性无关。
