# Nanotechnology and Early Human Development
## 4 Respiratory System
SP-A and SP-D are large hydrophilic glycoproteins involved in pulmonary host defense through binding to inhaled particles and pathogens. SP-B and SP-C are smaller hydrophobic proteins that regulate the very low surface tension observed in the lung. The expression of surfactant proteins is regulated by genetic and environmental factors, including inflammation [13; 14]. Interactions between surfactant and nanoparticles depend on the physico-chemical properties of the nanoparticles and also on the molecular composition, dynamic surface phase behavior, and monolayer biomechanics of the pulmonary surfactant [15; 16; 17]. The interaction between nanoparticles and surfactant has been studied with different methods. [PERSON] et al. [15] showed that many factors, including surface charge, degree of hydrophobicity, and acquisition of a lipoprotein corona from endogenous surfactant, influence nanoprotein adsorption and blood stream translocation. Hydrophobic nanoparticles, such as carbon-based nanomaterials, can be retained at the surfactant lining layer and can lead to increased inflammation. Hydrophilic nanoparticles can be used for systemic drug delivery due to their rapid absorption and translocation to other organs and tissues. Anionic nanoparticles may inhibit the biophysical function of pulmonary surfactant by binding to surfactant proteins and interfering with their functions. Cationic nanoparticles may be taken up by cells and may cause acute toxicity. Therefore, neutral nanoparticles might be the safest option for pulmonary drug delivery. In experimental models, some authors reported that hydrophilic nanomaterials (halloysite and bentonite) induced concentration-dependent damage on surfactant phospholipid function [18]. The shape and porous structure of nanoparticles are important factors to consider. Other authors found that nanoparticles have different effects on lung inflammation and function depending on their metal properties: compared to non-metal nanoparticles (which elicit a dose-dependent inflammatory effect), silver nanoparticles do not induce significant inflammation, but only change in lung elastance [19; 20]. On the other hand, the interaction between nanoparticles and surfactant may offer important therapeutic advantages: delivering drugs or nanoparticles in combination with surfactant can improve drug stability and prevent degradation and clearance in vivo, thereby allowing the delivery of macromolecular drugs. For example, nanovesicles carrying antibiotics have been successfully tested in animal models and clinical trials are ongoing [21; 22]. Other potential applications include the diagnosis and therapy of different pulmonary diseases, vaccines, and cancer therapy. Surfactant itself (animal-derived or synthetic) is an established therapy for respiratory distress syndrome, particularly among newborns: the administration of this drug is invasive, as it requires endotracheal instillation through a tube or a catheter. However, this maneuver can be associated with lung function deterioration and long-term complications among infants, and studies aimed at finding the most convenient method of administration are ongoing [23; 24]. Other potential applications include the diagnosis and therapy of different pulmonary diseases, vaccines, and cancer therapy. Some authors designed inhalable nanoparticles mimicking some of the lipid components of surfactant [25]. Hopefully, technological advancement in this field will eventually lead to the production of inhalable surfactant preparations, and invasive surfactant administration will eventually be overcome. Respiratory tract infections are among the most frequent worldwide and represent one of the most important causes of death in childhood. Antimicrobial resistance is a major challenge, as it results in increased morbidity and mortality worldwide. Since the development of new antimicrobials is expensive and has scarce success, one strategy to overcome this issue could be the application of synthetic products with antimicrobial properties.