Silica encapsulation of ZnO nanoparticles reduces their toxicity for cumulus cell-oocyte-complex expansion

Background Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion. Methods Mouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated. Results We show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low. Conclusions Altogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity

Towards an indicator of nanomaterial deposition in the human lung Nanotubes

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Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim In the last decade, along with the increasing use of graphene oxide (GO) in various applications, there is also considerable interest in understanding its effects on human health. Only a few experimental approaches can simulate common routes of exposure, such as ingestion, due to the inherent complexity of the digestive tract. This study presents the synthesis of size-sorted GO of sub-micrometer- or micrometer-sized lateral dimensions, its physicochemical transformations across mouth, gastric, and small intestinal simulated digestions, and its toxicological assessment against a physiologically relevant, in vitro cellular model of the human intestinal epithelium. Results from real-time characterization of the simulated digestas of the gastrointestinal tract using multi-angle laser diffraction and field-emission scanning electron microscopy show that GO agglomerates in the gastric and small intestinal phase. Extensive morphological changes, such as folding, are also observed on GO following simulated digestion. Furthermore, X-ray photoelectron spectroscopy reveals that GO presents covalently bound N-containing groups on its surface. It is shown that the GO employed in this study undergoes reduction. Toxicological assessment of the GO small intestinal digesta over 24 h does not point to acute cytotoxicity, and examination of the intestinal epithelium under electron microscopy does not reveal histological alterations. Both sub-micrometer- and micrometer-sized GO variants elicit a 20% statistically significant increase in reactive oxygen species generation compared to the untreated control after a 6 h exposure

Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim In the last decade, along with the increasing use of graphene oxide (GO) in various applications, there is also considerable interest in understanding its effects on human health. Only a few experimental approaches can simulate common routes of exposure, such as ingestion, due to the inherent complexity of the digestive tract. This study presents the synthesis of size-sorted GO of sub-micrometer- or micrometer-sized lateral dimensions, its physicochemical transformations across mouth, gastric, and small intestinal simulated digestions, and its toxicological assessment against a physiologically relevant, in vitro cellular model of the human intestinal epithelium. Results from real-time characterization of the simulated digestas of the gastrointestinal tract using multi-angle laser diffraction and field-emission scanning electron microscopy show that GO agglomerates in the gastric and small intestinal phase. Extensive morphological changes, such as folding, are also observed on GO following simulated digestion. Furthermore, X-ray photoelectron spectroscopy reveals that GO presents covalently bound N-containing groups on its surface. It is shown that the GO employed in this study undergoes reduction. Toxicological assessment of the GO small intestinal digesta over 24 h does not point to acute cytotoxicity, and examination of the intestinal epithelium under electron microscopy does not reveal histological alterations. Both sub-micrometer- and micrometer-sized GO variants elicit a 20% statistically significant increase in reactive oxygen species generation compared to the untreated control after a 6 h exposure

Printer center nanoparticles alter the DNA repair capacity of human bronchial airway epithelial cells

Nano-enabled, toner-based printing equipment emit nanoparticles during operation. The bioactivity of these nanoparticles as documented in a plethora of published toxicological studies raises concerns about their potential health effects. These include pro-inflammatory effects that can lead to adverse epigenetic alterations and cardiovascular disorders in rats. At the same time, their potential to alter DNA repair pathways at realistic doses remains unclear. In this study, size-fractionated, airborne particles from a printer center in Singapore were sampled and characterized. The PM0.1 size fraction (particles with an aerodynamic diameter less than 100 nm) of printer center particles (PCP) were then administered to human lung adenocarcinoma (Calu-3) or lymphoblastoid (TK6) cells. We evaluated plasma membrane integrity, mitochondrial activity, and intracellular reactive oxygen species (ROS) generation. Moreover, we quantified DNA damage and alterations in the cells' capacity to repair 6 distinct types of DNA lesions. Results show that PCP altered the ability of Calu-3 cells to repair 8oxoG:C lesions and perform nucleotide excision repair, in the absence of acute cytotoxicity or DNA damage. Alterations in DNA repair capacity have been correlated with the risk of various diseases, including cancer, therefore further genotoxicity studies are needed to assess the potential risks of PCP exposure, at both occupational settings and at the end-consumer level.Nanyang Technological UniversitySubmitted/Accepted versionReported research has received support from the Nanyang Technological University-Harvard T. H. Chan School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano; NTU-HSPH 18001). Engineered nanomaterials used in the research were characterized by the Engineered Nanomaterials Resource and Coordination Core established at Harvard T. H. Chan School of Public Health (NIH grant # U24ES026946) as part of the Nanotechnology Health Implications Research (NHIR) Consortium. Z.D.N. and S.M.T. were supported by U01ES029520, and Z.D.N. was also supported by P30ES000002. Partial funding for D.B. was provided by the International Initiative for the Environment and Public Health Cyprus Program at the Harvard School of Public Health. QH was supported by China Scholarship Council #201804910248

Co-exposure to the food additives SiO2 (E551) or TiO2 (E171) and the pesticide boscalid increases cytotoxicity and bioavailability of the pesticide in a tri-culture small intestinal epithelium model : potential health implications

Many toxicity investigations have evaluated the potential health risks of ingested engineered nanomaterials (iENMs); however, few have addressed the potential combined effects of iENMs and other toxic compounds (e.g. pesticides) in food. To address this knowledge gap, we investigated the effects of two widely used, partly nanoscale, engineered particulate food additives, TiO2 (E171) and SiO2 (E551), on the cytotoxicity and cellular uptake and translocation of the pesticide boscalid. Fasting food model (phosphate buffer) containing iENM (1% w/w), boscalid (10 or 150 ppm), or both, was processed using a simulated in vitro oral-gastric-small intestinal digestion system. The resulting small intestinal digesta was applied to an in vitro tri-culture small intestinal epithelium model, and effects on cell layer integrity, viability, cytotoxicity and production of reactive oxygen species (ROS) were assessed. Boscalid uptake and translocation was also quantified by LC/MS. Cytotoxicity and ROS production in cells exposed to combined iENM and boscalid were greater than in cells exposed to either iENM or boscalid alone. More importantly, translocation of boscalid across the tri-culture cellular layer was increased by 20% and 30% in the presence of TiO2 and SiO2, respectively. One possible mechanism for this increase is diminished epithelial cell health, as indicated by the elevated oxidative stress and cytotoxicity observed in co-exposed cells. In addition, analysis of boscalid in digesta supernatants revealed 16% and 30% more boscalid in supernatants from samples containing TiO2 and SiO2, respectively, suggesting that displacement of boscalid from flocculated digestive proteins by iENMs may also contribute to the increased translocation.Nanyang Technological UniversityAccepted versionSupport for the research was provided by (NIEHS grant # U24ES026946) as part of the Nanotechnology Health Implications Research Consortium, the Nanyang Technological University-Harvard T. H. Chan School of Public Health Initiative for Sustainable Nanotechnology and the HSPH-NIEHS Environmental Health Center Grant (grant # ES-000002). The engineered nanomaterials used in the research presented in this publication were characterized and provided by the Engineered Nanomaterials Resource and Coordination Core established at Harvard T. H. Chan School of Public Health (NIH grant # U24ES026946) as part of the Nanotechnology Health Implications Research Consortium. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health