Inflammatory Changes in Lung Tissues Associated with Altered Inflammation-Related MicroRNA Expression after Intravenous Administration of Gold Nanoparticles in Vivo

Abstract

Potential adverse effects of gold nanoparticles (AuNPs) are gaining attention due to their wide industrial, consumer, and biomedical applications. This may give rise to possible health risks from direct exposure to the NPs. Excessive inflammatory response is known to be one of the main effects induced by NPs. In this study, inflammatory and miRNA expression changes in lung tissues were evaluated in rats following intravenous administration of AuNPs. AuNPs (20 nm) at a mass concentration of 256 μg/mL were intravenously injected into 6–8 week old male Wistar rats at single doses of 0.025, 0.05, 0.1, and 0.2 mg/kg and sacrificed at 1 week, 1 month, and 2 months, respectively. The biodistribution of AuNPs in the lungs of the rats was determined by inductively coupled plasma mass spectrometry. There were no apparent changes observed in the body weight of the experimental rats. Histopathological examination revealed the presence of infiltrating lymphocytes in lung interstitial tissues and enhanced IL-1α immunostaining in the lung tissues. Out of 84 rat microRNAs (miRNAs) analyzed, the expression of three miRNAs in rat lungs were dysregulated by more than 2-fold in the 0.1 and 0.2 mg/kg AuNP-treated rats 1 week after exposure. In particular, miR-327 was significantly down-regulated in both groups of treated rats. Taken together, it would seem that miRNAs may regulate inflammatory changes in the lungs after exposure to AuNPs in vivo.

Gold nanostructures: synthesis, properties, and neurological applications

“…From a mechanical point of view, it was demonstrated that the AuNPs caused the downregulation of microRNA (miRNA)-327, resulting in higher levels of lung inflammation. 213 Other in vivo studies have found similar results, where IV administration of PEGylated AuNPs into mice was found to result in altered levels of miRNA-183 and let-7a in the lung and liver, correlating with inflammatory responses. 214 The fact that AuNPs cause oxidative stress has been widely reported.…”

Main trends of immune effects triggered by nanomedicines in preclinical studies

“…Oxidative stress generation, interaction with toll-like receptors, responsible for pathogen recognition, and activation of inflammatory pathways such as cellular nuclear factor-κB were pointed out as main mechanisms of NP-induced inflammation. [16][17][18][19] The inflammatory reactions were almost exclusively induced by inorganic NPs, mainly carbon-based or metal-based NPs, in particular, titanium dioxide NPs, gold NPs, 20,21 silica NPs 22 and graphene oxidebased nanomaterials. 23,24 An important component of the innate immune defense consists of the macrophages covering heterogeneous population of phagocytic cells.…”

“…• Activation of inflammatory pathways 17,24,27 • Histopathology 20,23,55 • Production of ROS and RNS 22,119,120 Rodents Partially covered by ICH S8 as a part of STS…”

Safety Assessment of Nanomaterials for Antimicrobial Applications

“…They described that the translocation of AuNPs in neonates was higher irrespective of the particle size, while in adults, translocation was less and size-dependent, which shows the vulnerability of infancy in terms of lung damage . Ng et al showed the Au NPs’ impacts on inflammation and miRNA expression changes in rats after intravenous administration, indicating that the importance of the biological effect of NPs cannot be ignored. Ma et al used polymer-coated AuNPs, where internalization of NPs showed abnormalities in important intracellular structures and activities such as mitochondrial morphology, lysosomal enlargement, the disordering of actin and tubulin cytoskeleton, and related signaling .…”