Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95125 Catania, Italy.
Int J Mol Sci. 2021 Mar 7;22(5):2694. doi: 10.3390/ijms22052694.
Carbon-based nanomaterials are nowadays attracting lots of attention, in particular in the biomedical field, where they find a wide spectrum of applications, including, just to name a few, the drug delivery to specific tumor cells and the improvement of non-invasive imaging methods. Nanoparticles inhaled during breathing accumulate in the lung alveoli, where they interact and are covered with lung surfactants. We recently demonstrated that an apparently non-toxic concentration of engineered carbon nanodiamonds (ECNs) is able to induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells. Therefore, the complete understanding of their "real" biosafety, along with their possible combination with other molecules mimicking the in vivo milieu, possibly allowing the modulation of their side effects becomes of utmost importance. Based on the above, the focus of the present work was to investigate whether the cellular alterations induced by an apparently non-toxic concentration of ECNs could be counteracted by their incorporation into a synthetic lung surfactant (DPPC:POPG in 7:3 molar ratio). By using two different cell lines (alveolar (A549) and microglial (BV-2)), we were able to show that the presence of lung surfactant decreased the production of ECNs-induced nitric oxide, total reactive oxygen species, and malondialdehyde, as well as counteracted reduced glutathione depletion (A549 cells only), ameliorated cell energy status (ATP and total pool of nicotinic coenzymes), and improved mitochondrial phosphorylating capacity. Overall, our results on alveolar basal epithelial and microglial cell lines clearly depict the benefits coming from the incorporation of carbon nanoparticles into a lung surfactant (mimicking its in vivo lipid composition), creating the basis for the investigation of this combination in vivo.
目前，碳基纳米材料备受关注，尤其在生物医药领域，其应用广泛，如靶向特定肿瘤细胞的药物输送和非侵入性成像方法的改进。纳米颗粒在呼吸过程中吸入后会在肺泡中积累，在那里与肺表面活性剂相互作用并被其覆盖。我们最近证明，浓度明显低于毒性的工程碳纳米金刚石（ECN）能够诱导小胶质细胞和肺泡基底上皮细胞发生氧化/硝化应激、能量代谢失衡和线粒体功能障碍。因此，深入了解其“真正”的生物安全性，以及它们与其他模拟体内环境的分子结合的可能性，从而可能调节其副作用，变得至关重要。基于此，本研究的重点是研究浓度明显低于毒性的 ECN 能否通过掺入合成肺表面活性剂（DPPC：POPG 摩尔比为 7:3）来逆转细胞的改变。通过使用两种不同的细胞系（肺泡（A549）和小胶质细胞（BV-2）），我们能够证明肺表面活性剂的存在降低了 ECN 诱导的一氧化氮、总活性氧和丙二醛的产生，并逆转了谷胱甘肽的消耗（仅在 A549 细胞中），改善了细胞能量状态（ATP 和烟酰胺辅酶的总池），并提高了线粒体磷酸化能力。总的来说，我们在肺泡基底上皮细胞和小胶质细胞系上的研究结果清楚地描绘了将碳纳米颗粒掺入肺表面活性剂（模拟其体内脂质组成）所带来的好处，为研究这种体内结合奠定了基础。
