Dataset Information

Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

ABSTRACT: Do immature lungs have air-blood barriers that are more permeable to inhaled nanoparticles than those of fully developed mature lungs? Data supporting this notion and explaining the underlying mechanisms do not exist as far as we know. Using a rat model of postnatal lung development, here the data exactly supporting this notion, that is, significantly more gold nanoparticles (NPs) cross from the air space of the lungs to the rest of the body in neonates than in adults, are presented. Moreover, in neonates the translocation of gold NPs is not size dependent, whereas in adult animals smaller NPs cross the air-blood lung barrier much more efficiently than larger NPs. This difference in air-blood permeability in neonate versus adult animals suggests that NP translocation in the immature lungs may follow different rules than in mature lungs. Supporting this notion, we propose that the paracellular transport route may play a more significant role in NP translocation in immature animals, as suggested by protein expression studies. Findings from this study are critical to design optimal ways of inhalation drug delivery using NP nanocarriers for this age group, as well as for better understanding of the potential adverse health effects of nanoparticle exposures in infants and young children.

SUBMITTER: Tsuda A

PROVIDER: S-EPMC6929694 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

Tsuda Akira A Donaghey Thomas C TC Konduru Nagarjun V NV Pyrgiotakis Georgios G Van Winkle Laura S LS Zhang Zhenyuan Z Edwards Patricia P Bustamante Jessica-Miranda JM Brain Joseph D JD Demokritou Phillip P

ACS nano 20190816 9

Do immature lungs have air-blood barriers that are more permeable to inhaled nanoparticles than those of fully developed mature lungs? Data supporting this notion and explaining the underlying mechanisms do not exist as far as we know. Using a rat model of postnatal lung development, here the data exactly supporting this notion, that is, significantly more gold nanoparticles (NPs) cross from the air space of the lungs to the rest of the body in neonates than in adults, are presented. Moreover, i ...[more]

PMID: 31397554

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Project description:BackgroundThere is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels.MethodsWe intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm ¹??AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled ¹??AuNP after 24 hours.ResultsWe observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of ¹??AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes.ConclusionOur data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels - also present in the human placenta - and/or (2) endocytotic and diffusive processes across the placental barrier.

Dataset Information

Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

Publications

Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

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