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

Giuseppe Caruso,Angelita Costantino,Susan M Lunte,Angela M Amorini,Massimo Gulisano,Giuseppe Lazzarino,Barbara Tavazzi,Claudia G Fresta,Prajnaparamita Dhar,Giacomo Lazzarino,Filippo Caraci

doi:10.3390/ijms22052694

Abstract

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.

Highlights

The ideas and concepts behind nanotechnology, initially defined as the process in which scientists would be able to manipulate and control individual atoms and molecules, were first introduced by Nobel laureate Richard Feyman during his famous lecture entitled “There’s Plenty of Room at the Bottom” in the late 1950s [1]
We recently evaluated in alveolar basal epithelial (A549) and brain microglial (BV-2) cells, whether an apparently non-toxic concentration of engineered carbon nanodiamonds (ECNs) was able to cause cellular biochemical alterations
Under these experimental sub-toxic conditions, we found that ECNs-challenged cells underwent an increase in nitric oxide (NO) and reactive oxygen species (ROS) production, as well as a deregulation of mitochondrial functions and energetic metabolism [23]

Summary

Introduction

The ideas and concepts behind nanotechnology, initially defined as the process in which scientists would be able to manipulate and control individual atoms and molecules, were first introduced by Nobel laureate Richard Feyman during his famous lecture entitled “There’s Plenty of Room at the Bottom” in the late 1950s [1]. The increased specific surface area allows these particles to transport therapeutic agents, biomarkers, and ligands more efficiently, as compared to the conventional drug delivery systems, having the potential to radically change the method of administering drugs [11]. Considering the carbon-based nanoparticles, non-toxic diamond nanoparticles (engineered carbon nanodiamonds, ECNs) represent very promising drug delivery vehicles allowing greater treatment sensitivity and more patient-specific dosages [12,13,14,15,16]. There is a “but”; despite their enormous potential in terms of applications, some aspects concerning the possible toxicity and side effects of nanoparticles, the complexity in the management of drug administration (nanodiamond/drug interface), or the difficulty of purifying the nanodiamonds with a high yield have not yet been clarified [11]

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Conclusion