Inhaled Nanoparticles Accumulate at Sites of Vascular Disease

Abstract

The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2–200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.

Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRD

“…30 The third (and most plausible hypothesis) is predicated on the premise that airborne particulates enter the bloodstream where they may then interact with tissue components to promote the observed pathologic effects 30,31 ; the latter is supported by emerging evidence suggesting that inhaled inert gold nanoparticles not only enter the bloodstream of healthy adult volunteers, but are detected in the urine within minutes after exposure, providing a proof of concept that inhaled nanoparticles get filtered and excreted by the kidney. 31 These three hypotheses provide contextual background to evaluate the experimental and clinical findings describing the extrapulmonary effect of particulate matter air pollution, where it has been reported that exposure to elevated levels of PM 2.5 is associated with increased inflammatory mediators (including TNF-a, IL-6, and plasminogen activator inhibitor-1), oxidative stress, [32][33][34] increased atherosclerotic plaque area, and exaggerated vasoconstrictor responses to phenylephrine and serotonin. 35 Evidence suggests that increased PM 2.5 concentrations are associated with significant decrease in flow-mediated dilatation, 36,37 increases in systolic BP and pulse pressure, [38][39][40] and disturbances in the hypothalamic-pituitary-adrenal axis.…”

Pre‐natal brain development as a target for urban air pollution

“…[40][41][42][43][44][45][46] Impairing placental function and decreasing transplacental oxygen and nutrient transport could be among potential mechanisms by which air pollution could affect foetal brain development during pregnancy. Evidence from birth cohorts suggests that air pollution affects placental function measured by Doppler ultrasound (negative effects on umbilical artery resistance in one study, 41 but not in another 42 during the second and third trimester; and negative associations on flow indices in the first trimester 47 ). There is consistent evidence that impaired placental function disrupts foetal neurodevelopment in animals and neurobehavioural development in children.…”

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

“…Phe is known to exert direct toxicity in dogs where aerosolized Phe was rapidly transported into the bloodstream following inhalation (Gerde et al 1993). Particle translocation may also assist the passage of Phe within PM to areas of susceptibility, given that translocated nanoparticles have been shown to preferentially accumulate at sites of vascular disease (Miller et al 2017a).…”

“…Particle translocation may also assist the passage of Phe within PM to areas of susceptibility, given that translocated nanoparticles have been shown to preferentially accumulate at sites of vascular disease (Miller et al . ).…”

“…However, experimental studies using model nanoparticles such as radiolabelled carbon or gold nanoparticles have robustly demonstrated that this pathway occurs in rodents (Geiser & Kreyling, ) and now recently in humans (Miller et al . , b ). The translocation pathway is of importance as it provides a biological basis that could account for the widespread effects of inhaled PM across the CVS, and elsewhere in the body (Raftis & Miller, ).…”