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Titanium dioxide nanoparticles (TiO2 NPs) are authorized food additives, and children have the highest exposure. Therefore, children are likely more susceptible to the adverse effects of TiO2 NPs than adults. Previous study showed that oral administration of 50 mg/kg body weight (bw) TiO2 NPs increase plasma glucose in mice. However, few studies have directly compared the adverse effects of exposure to TiO2 NPs on plasma glucose metabolism of different age groups. In this study, the developing (age 3 weeks) and adult mice (age 10 weeks) were orally administered with 50 mg/kg bw TiO2 NPs per day. The TiO2 NPs induced hyperglycemia earlier in the developing mice than in the adult mice. Then mechanisms were analyzed after mice were oral administration of TiO2 NPs for 8 weeks and 26 weeks, respectively. Results showed that the treatment with TiO2 NPs activated xenobiotic biodegradation in livers of both developing and adult mice at the early stage. However, only in the developing mice, TiO2 NPs induced endoplasmic reticulum (ER) stress in livers and increased reactive oxygen species in livers and sera in the early stage. The ER stress and ROS activated an inflammation response and mitogen‐activated protein kinase pathways, thereby inducing insulin resistance in the livers of developing mice at the early stage. The response of the adult mice was delayed, and these changes were observed in the late stage of the study. The results of this study all suggest that children are more susceptible than adults to the toxicity of orally administered TiO2 NPs. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO NPs) represent an important class of commercially applied materials. Recently, adverse effects of ZnO NPs were found in humans and animals following ingestion, although the effects on endocrine system disease remain unclear. In this study, ZnO NPs were orally administered to mice, and at doses of 25 mg/kg bw (body weight) ZnO NPs and above, plasma glucose increased significantly. The genome-wide effects of ZnO NPs were then investigated using RNA-sequencing technology. In the cluster analysis, the most significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways concerned membranes and their close association with endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation. Biochemical and gene and protein expression analyses revealed that ZnO NPs activated a xenobiotic biodegradation response and increased the expression of cytochrome P450 (CYP) enzymes in mice livers, leading to ER stress. The ER stress increased ROS generation. The high levels of ROS activated the MAPK and NF-κB pathways and induced an inflammation response, resulting in the phosphorylation of insulin receptor substrate 1. Thus, the insulin resistance that developed was the primary mechanism for the increase in the plasma glucose of mice treated orally with ZnO NPs. [ABSTRACT FROM AUTHOR]

Based on our previous work on the PLGA nanoparticles modified with biotinylated chitosan (Bio-CS-PLGA NPs), we further studied the stability, toxicity, pharmacokinetics, andin vivoefficacy. The safety of NPs was studied through single-dose toxicity test in mice, and the result showed that NPs were well tolerated at the dose of 300 mg/kg. Compared with the free EPB group, the NPs group exhibited higher plasma drug concentration, longer half-life time. EPB-loaded NPs significantly inhibited the tumor growth compared to free EPB. All results suggested that Bio-CS-PLGA NPs were stable, safe, and showed a promising potential on targeted drug delivery. [ABSTRACT FROM AUTHOR]