Lung Surfactant Decreases Biochemical Alterations and Oxidative Stress Induced by a Sub-Toxic Concentration of Carbon Nanoparticles in Alveolar Epithelial and Microglial Cells.


Caruso G(1), Fresta CG(2), Costantino A(1)(3), Lazzarino G(4), Amorini AM(2), Lazzarino G(2), Tavazzi B(5)(6), Lunte SM(7)(8)(9), Dhar P(8)(10), Gulisano M(1)(3)(11), Caraci F(1)(12).
Author information:
(1)Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
(2)Department of Biomedical and Biotechnological Sciences
(BIOMETEC), University of Catania, 95125 Catania, Italy.
(3)Interuniversity Consortium for Biotechnology, Area di Ricerca, Padriciano, 34149 Trieste, Italy.
(4)UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy.
(5)Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, 00168 Rome, Italy.
(6)Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
(7)Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA.
(8)Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA.
(9)Department of Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA.
(10)Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS 66045-7576, USA.
(11)Molecular Preclinical and Translational Imaging Research Centre-IMPRonTE, University of Catania, 95125 Catania, Italy.
(12)Oasi Research Institute-IRCCS, 94018 Troina
(EN), Italy.


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.