Promoting effects of nanoparticles/materials on sensitive lung inflammatory diseases

Abstract

Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully established. We provide insights into the environmental immunotoxicity of nanoparticles as an aggravating factor in hypersusceptible subjects, especially those with respiratory disorders, using our in vivo models. We first examined the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide) as a test model against innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate lung inflammation. Secondly, we examined the effects of nanoparticles/materials on allergic pathophysiology, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations

“…Subsequently, as the GNP-Dex is absorbed into the circulation, the vasoconstriction is cleared, allowing blood pressure measurement. Based on these results and other literature reports [39–42], we hypothesize the following as the cause of observed mortality at the higher doses (> 125 mg/kg). As GNP-Dex gets into pulmonary micro- circulation during the first pass, a large number of nanoparticles in the very small diameter of the micro vessels (<100 μm) [43] could occlude blood vessel, hamper blood flow in the systemic circulation, and ultimately induce cardiac arrest.…”

Current understanding of interactions between nanoparticles and the immune system

“…Moreover, some nanomaterials, while not inflammatory themselves, were able to potentiate endotoxin-mediated inflammation. Silica- and carbon-based nanomaterials, as well as some metal oxides, have been shown to exaggerate endotoxin-mediated inflammation in the lungs (Inoue et al, 2006; Inoue et al, 2007; Shi et al, 2010; Inoue, 2011; Inoue and Takano, 2011), while cationic PAMAM dendrimers were reported to exaggerate endotoxin-induced leukocyte PCA (Dobrovolskaia et al, 2012; Ilinskaya et al, 2014). Strategies for endotoxin detection have been discussed elsewhere (Dobrovolskaia, 2015).…”

Inhibition of Phosphoinositol 3 Kinase Contributes to Nanoparticle-Mediated Exaggeration of Endotoxin-Induced Leukocyte Procoagulant Activity

“…For example, G6 cationic PAMAM dendrimers enhanced PCA [13], TiO 2 nanobelts and carbon-based nanoparticles enhanced in vitro cytokine response and in vivo lung inflammation [24–26], and amorphous silica nanoparticles exaggerated oxidative-stress-mediated reactions [27]. Since engineered nanomaterials are becoming increasingly more prevalent in the development of drug-delivery platforms and since endotoxin contamination and its detection represent a challenge for these materials, it is imperative to understand which nanoparticle physicochemical properties are responsible for the exaggeration of endotoxin-mediated toxicities [22,23,28].…”