Given that the effects of ultrafine fractions (<0.1 μm) on ischemic heart diseases (IHD) and other cardiovascular diseases are gaining attention, this study is aimed to explore the influence of silica nanoparticles (SiNPs)-induced autophagy on endothelial cell homeostasis and angiogenesis. Ultrastructural changes of autophagy were observed in both vascular endothelial cells and pericytes in the heart of ICR mice by TEM. Autophagic activity and impaired angiogenesis were further confirmed by the immunohistochemistry staining of LC3 and VEGFR2. In addition, the immunohistochemistry results showed that SiNPs had an inhibitory effect on ICAM-1 and VCAM-1, but no obvious effect on E-selectin in vivo. The disruption of F-actin cytoskeleton occurred as an initial event in SiNPs-treated endothelial cells. The depolarized mitochondria, autophagic vacuole accumulation, LC3-I/LC3-II conversion, and the down-regulation of cellular adhesion molecule expression were all involved in the disruption of endothelial cell homeostasis in vitro. Western blot analysis indicated that the VEGFR2/PI3K/Akt/mTOR and VEGFR2/MAPK/Erk1/2/mTOR signaling pathway was involved in the cardiovascular toxicity triggered by SiNPs. Moreover, there was a crosstalk between the VEGFR2-mediated autophagy signaling and angiogenesis signaling pathways. In summary, the results demonstrate that SiNPs induce autophagic activity in endothelial cells and pericytes, subsequently disturb the endothelial cell homeostasis and impair angiogenesis. The VEGFR2-mediated autophagy pathway may play a critical role in maintaining endothelium and vascular homeostasis. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by nano-sized particles.

Background: Quantum dots (QDs) have been used as novel fluorescent nanoprobes for various bioapplications. The degradation of QDs, and consequent release of free cadmium ions, have been suggested to be the causes of their overall toxicity. However, in contrast to sufficient investigations regarding the biological fate of QDs, a paucity of studies have reported their chemical fate in vivo. Therefore, the overall aim of our study was to understand the chemical fate of QDs in vivo and explore analytical techniques or methods that could be used to define the chemical fate of QDs in vivo. Methods: Male ICR mice were administered a single intravenous dose (0.2 μmol/kg) of aqueous synthesized CdTe/ZnS aqQDs. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to simultaneously measure the concentrations of cadmium (Cd) and tellurium (Te) in the blood and tissues over the course of a 28 day period. We compared the blood kinetic parameters and biodistributions of Cd and Te, and used the molar ratio of Cd:Te as a marker for QDs degradation. Results: Cd and Te display different blood kinetics and biodistribution profiles. The Cd:Te ratio in the blood did not vary significantly within the first hour compared with intact CdTe/ZnS aqQDs. The Cd:Te ratio decreased gradually over time from the 6 h time point on. Cd accumulated in the liver, kidneys, and spleen. Te was distributed primarily to the kidneys. Sharp time-dependent increases in the Cd:Te ratio were found in liver tissues. Conclusions: QDs can undergo degradation in vivo. In vitro, QDs are chemically stable and do not elicit the same biological responses or consequences as they do in vivo. Our methods might provide valuable information regarding the degradation of QDs in vivo and may enable the design and development of QDs for biological and biomedical applications.

Dose and time effect of CdTe quantum dots on antioxidant capacities of the liver and kidneys in mice Jilong Wang,1,2,* Hubo Sun,1,2,* Peijun Meng,1,2 Mengmeng Wang,1,2 Mi Tian,3 Yamin Xiong,1,2 Xueying Zhang,1,2 Peili Huang1,2 1School of Public Health, Capital Medical University, 2Beijing Key Laboratory of Environmental Toxicology, 3Medical Experiment and Test Center, Capital Medical University, Beijing, Peopleâ??s Republic of China *These authors contributed equally to this work Although quantum dot (QD)-induced toxicity occurs due to free radicals, generation of oxidative stress mediated by reactive oxygen species (ROS) formation is considered an important mechanism. However, free radical mechanisms are essentially difficult to elucidate at the molecular level because most biologically relevant free radicals are highly reactive and short-lived, making them difficult to directly detect, especially in vivo. Antioxidants play an important role in preventing or, in most cases, limiting the damage caused by ROS. Healthy people and animals possess many endogenous antioxidative substances that scavenge free radicals in vivo to maintain the redox balance and genome integrity. The antioxidant capacity of an organism is highly important but seldom studied. In this study, the dose and time effects of CdTe QDs on the antioxidant capacities of the liver and kidneys were investigated in mice using the electron paramagnetic resonance (EPR) spin-trapping technique. We found that the liver and kidneys of healthy mice contain specific antioxidant capacities that scavenge ·OH and ·O2-. Furthermore, oxidative stress markers (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], glutathione [GSH] and malondialdehyde [MDA]) were examined. In dose course studies, the free radical scavenging efficiencies of the liver and kidneys were found to gradually decrease with increasing concentration of CdTe QD exposure. The activities and levels of SOD, CAT, GPx and MDA were observed to increase in treated groups, whereas those of GSH were reduced. The time course studies revealed that the QD-induced antioxidant efficiency reduction was time dependent with GSH decrease and could recover after a period of time. These experimental results offer new information on QD toxicity in vivo. Specifically, CdTe QDs can deplete GSH to reduce the elimination ability of the liver and kidneys for ·OH and ·O2-, thus inducing oxidative damage to tissues. Keywords: quantum dot, antioxidative capacity, free radical elimination, hydroxyl radical, superoxide anion radical, spin-trappingÂ

With the detection of nano-plastics (NPs) in daily essentials and drinking water, the potential harm of NPs to human health has become the focus of global attention. Studies have shown that long term exposure to NPs can lead to disorders of glucose and lipid metabolism in organisms, while the effects of short term exposure are rarely reported. Moreover, environmental factors cause the aging of NPs, and it is unclear whether this has an effect on their toxicity. In this study, we use 100 nm polystyrene (PS) NPs and ultraviolet (UV) aging PS (aPS) NPs to gavage mice for 7 days at an exposure dose of 50 mg/kg/day. To evaluate the effects of exposure on mice hepatic glucose lipid metabolism, we performed blood biochemical, pathological and metabolomic analyses. The results showed that exposure to PS NPs and aPS NPs increased serum glucose, disrupted serum lipoprotein levels, and up-regulated the expression levels of phosphatidylinositol 3-kinase (PI3K)/ phosphoprotein kinase B (p-AKT)/Glucose transporter 4 (GLUT4) proteins in the glucose metabolism pathway. The expression levels of key proteins sterol regulatory element binding protein-1 (SREBP-1)/peroxisome proliferator-activated receptor-γ (PPARγ)/adipose triglyceride lipase (ATGL) in the lipid metabolism signaling pathway were significantly increased. These findings suggest that short term exposure to PS NPs and aPS NPs induces glycolipid metabolism disturbance in mice, which may subsequently awaken the mice to self-regulate the serum levels of various lipoproteins and the expression of related key proteins. Compared with PS NPs, the aPS NPs interfered more strongly with glucose metabolism, and the corresponding self-regulation in mice was also more obvious. These findings not only provide a basis for environmental factors to increase the health risk of NPs but also provided a reference for the selection of test substances for further studies on the toxicity of NPs.

A complete understanding of the toxicological behavior of quantum dots (QDs) in vivo is of great importance and a prerequisite for their application in humans. In contrast with the numerous cytotoxicity studies investigating QDs, only a few in vivo studies of QDs have been reported, and the issue remains controversial. Our study aimed to understand QD-mediated toxicity across different time points and to explore the roles of free cadmium ions (Cd²⁺) and hydroxyl radicals (·OH) in tissue damage. Male ICR mice were administered a single intravenous dose (1.5 µmol/kg) of CdTe QDs, and liver and kidney function and morphology were subsequently examined at 1, 7, 14, and 28 days. Furthermore, ·OH production in the tissue was quantified by trapping ·OH with salicylic acid (SA) as 2,3-dihydroxybenzoic acid (DHBA) and detecting it using a high-performance liquid chromatography fluorescence method. We used the induction of tissue metallothionein levels and 2,3-DHBA:SA ratios as markers for elevated Cd²⁺ from the degradation of QDs and ·OH generation in the tissue, respectively. Our experimental results revealed that the QD-induced histopathological changes were time-dependent with elevated Cd²⁺ and ·OH, and could recover after a period of time. The Cd²⁺ and ·OH exhibited delayed effects in terms of histopathological abnormalities. Histological assessments performed at multiple time points might facilitate the evaluation of the biological safety of QDs.