Distribution of Silver Nanoparticles to Breast Milk and Their Biological Effects on Breast-Fed Offspring Mice

Morishita, Yuki; Yoshioka, Yasuo; Takimura, Yuya; Shimizu, Yuki; Namba, Yuki; Nojiri, Nao; Ishizaka, Takuya; Takao, Keizo; Yamashita, Fumiyoshi; Takuma, Kazuhiro; Ago, Yukio; Nagano, Kazuya; Mukai, Yohei; Kamada, Haruhiko; Tsunoda, Shin-ichi; Saito, Shigeru; Matsuda, Toshio; Hashida, Mitsuru; Miyakawa, Tsuyoshi; Higashisaka, Kazuma; Tsutsumi, Yasuo

doi:10.1021/acsnano.6b01782

Cited by 62 publications

(41 citation statements)

References 48 publications

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“…50) We consider that this information about the associations among the physicochemical properties and biological effects of nanoparticles could lead to clarification of the regulatory factors that define the biological effects or in vivo/in vitro kinetics of nanoparticles.…”

Section: Associations Among the Physicochemical Properties And Biologmentioning

confidence: 99%

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

Higashisaka

Nagano

Yoshioka

et al. 2017

Biological & Pharmaceutical Bulletin

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In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now an important part of our daily lives. Despite our increasing exposure to nanoparticles, however, information regarding the absorption, distribution, metabolism, excretion, and toxicity of nanoparticles remains limited. In this review, we introduce our group's ongoing research into the biological effects and toxicities of nanoparticles, which we broadly refer to as "nano-safety research." In addition to determining the biological effects of nanoparticles and elucidating the underlying mechanisms of those effects, we are also exploring the associations among the physicochemical properties and kinetics of nanoparticles. Furthermore, we are currently developing a battery of biomarkers that we hope will be used to predict the biological effects of nanoparticles during the early stages of development. Our research provides valuable basic information on the safety of nanoparticles. We hope that this information will be used for the development of better assessments of nanoparticles safety and for the creation of more appropriate regulations to ensure not only the safety but also the sustainability of nanotechnology.

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Section: Associations Among the Physicochemical Properties And Biologmentioning

confidence: 99%

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

Higashisaka

Nagano

Yoshioka

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Currently, scientific efforts are concentrated on determining the effects of NPs on the female reproductive system and embryo development in vivo. 28,32,34,35,39,[43][44][45][46] Yamashita et al found that silica NPs could penetrate into the rodent placenta and transferred to the fetuses, resulting in structural and functional damages in the placenta as well as the inhibition of fetal growth. 23 Chu et al reported that prenatal exposure to CdTe/CdS QDs could migrate from pregnant mice to their fetuses across the placental barrier, 26 whereas we found that amphiphilic polymer-coated CdSe/ZnS QDs (20 nm) were effectively blocked by the placental barrier in our recent study.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, silver NPs were found in breast milk and in the brains of pups and it was also found that titanium dioxide NPs damaged the tight junction of the bloodmilk barrier. 44,45,47 However, these studies lacked biodistribution profiles of NPs in dams, gastrointestinal examination of NPs in pups, and a systemic growth and development analysis of offspring in the long term.…”

Section: Introductionmentioning

confidence: 99%

Quantum dots cause acute systemic toxicity in lactating rats and growth restriction of offspring

et al. 2018

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The in vivo toxicity of QDs in animals has been broadly studied; however, their reproductive toxicity towards lactating rodents is currently unknown. This study therefore aims to assess the potential toxicity against dams and offspring after postnatal QD exposure at two doses (5 and 1 nmol per rat) and unravel whether QDs can translocate to pups via breastfeeding. The dose-dependent systemic toxicity of QDs in dams was observed by examining the body weight, hematology, biochemistry, histopathological changes, and sex hormone levels. It was found that the QDs primarily accumulated in the liver and spleen of dams at 1 day post injection (dpi), but the highest concentrations were found in the kidneys at 18 dpi. A few QDs were detected in breast milk and stomach and intestine of pups; this suggested that the QDs were transmitted to breast milk via blood circulation and then transferred to pups via breastfeeding. High-dose QDs induced severe growth inhibition and a 71.08% offspring mortality, while pups showed growth restriction within 90 dpi in the low-dose group. Moreover, the hematology, biochemistry, and histology results showed limited chronic toxicity against offspring in the long term. This study provides a theoretical foundation for the exposure assessment of nanomaterials in lactating animals and for the advancement of QDs in the biomedical field.

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“…The first is their ability to cross biological barriers [e.g., blood–brain barrier (8), placental barrier (9), blood–milk barrier (10), and nuclear barrier (11)]. The second is their large surface area per unit mass due to their small particle size.…”

Section: Introductionmentioning

confidence: 99%

Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle Exposure Is Size Specific

et al. 2017

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The application of nanotechnology in the health care setting has many potential benefits; however, our understanding of the interactions between nanoparticles and our immune system remains incomplete. Although many of the biological effects of nanoparticles are negatively correlated with particle size, some are clearly size specific and the mechanisms underlying these size-specific biological effects remain unknown. Here, we examined the pro-inflammatory effects of silica particles in THP-1 cells with respect to particle size; a large overall size range with narrow intervals between particle diameters (particle diameter: 10, 30, 50, 70, 100, 300, and 1,000 nm) was used. Secretion of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced by exposure to the silica particles had a bell-shaped distribution, where the maximal secretion was induced by silica nanoparticles with a diameter of 50 nm and particles with smaller or larger diameters had progressively less effect. We found that blockade of IL-1β secretion markedly inhibited TNF-α secretion, suggesting that IL-1β is upstream of TNF-α in the inflammatory cascade induced by exposure to silica particles, and that the induction of IL-1β secretion was dependent on both the NLRP3 inflammasome and on uptake of the silica particles into the cells via endocytosis. However, a quantitative analysis of silica particle uptake showed that IL-1β secretion was not correlated with the amount of silica particles taken up by the cells. Further investigation revealed that the induction of IL-1β secretion and uptake of silica nanoparticles with diameters of 50 or 100 nm, but not of 10 or 1,000 nm, was dependent on scavenger receptor (SR) A1. In addition, of the silica particles examined, only those with a diameter of 50 nm induced strong IL-1β secretion via activation of Mer receptor tyrosine kinase, a signal mediator of SR A1. Together, our results suggest that the SR A1-mediated pro-inflammatory response is dependent on ligand size and that both SR A1-mediated endocytosis and receptor-mediated signaling are required to produce the maximal pro-inflammatory response to exposure to silica particles.

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Distribution of Silver Nanoparticles to Breast Milk and Their Biological Effects on Breast-Fed Offspring Mice

Cited by 62 publications

References 48 publications

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

Quantum dots cause acute systemic toxicity in lactating rats and growth restriction of offspring

Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle Exposure Is Size Specific

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