Search

The potential applications of nanomaterials used in nanomedicine as ingredients in drug delivery systems and in other products continue to expand. When nanomaterials are introduced into physiological environments and driven by energetics, they readily associate proteins forming a protein corona (PC) on their surface. This PC could result in an alteration of the nanomaterial’s surface characteristics, affecting their interaction with cells due to conformational changes in adsorbed protein molecules. However, our current understanding of nanobiological interactions is still very limited. Utilizing a liquid chromatography–mass spectroscopy/mass spectroscopy technology and a Cytoscape plugin (ClueGO) approach, we examined the composition of the PC for a set of zinc oxide nanoparticles (ZnONP) from cell culture media typically and further analyzed the biological interaction of identified proteins, respectively. In total, 36 and 33 common proteins were investigated as being bound to ZnONP at 5 min and 60 min, respectively. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Proteins bound to the surface of nanoparticles that may modify the structure, therefore the function of the adsorbed protein could be consequently affect the complicated biological processes.

Zinc Oxide nanoparticles (ZnO NPs) in its small size with large reactive surfaces can lead to toxicological injury by generating reactive oxygen species (ROS) and oxidative stress. Recently, ZnO NPs were shown to play a role in acute or chronic toxicities with mammalian cells, where its mechanism of toxicity is not fully characterized yet. In this study, the potential mechanisms of ZnO NPs in inducing and increasing oxidative stress for causing cellular apoptosis were investigated with human keratinocytes. Indeed, ZnO NPs induced significant intracellular ROS and mitochondrial ROS productions. And it seemed that cellular ROS levels induced by ZnO NPs led to the dissipation of the mitochondrial membrane potentials and elicited the cellular apoptosis. The induced ROS production by ZnO NPs was blocked with chelator treatment, which inhibited the ZnO ion. The present study demonstrates that increased levels of ROS by ZnO NPs cause mitochondrial dysfunction and cellular apoptosis.

Silica nanoparticles (NPs) are widely applied in many fields, such as chemical industry, medicine, cosmetics, and agriculture. However, the hazardous effects of silica NPs exposure are not completely understood. In this study, the two different sizes (20 nm and 100 nm) and different charges (negatively charged [NC] and weakly negatively charged [WNC]) of silica NPs were used. The present study investigated the cytotoxicity and reactive oxygen species (ROS) generation of silica NPs on keratinocytes. The phototoxicity test of silica NPs was performed on skin fibroblast cells. In addition, skin irritation and skin sensitization of silica NPs were studied on HSEM and mouse skin, respectively. The cell viability of NC 20 nm silica NPs was decreased. However, there are no cytotoxicity for NC 100 nm silica NPs and WNC silica NPs (20 and 100 nm). The results for silica NPs-induced ROS generation are consistent with the cytotoxicity test by silica NPs. Further, NC and WNC silica NPs induced no phototoxicity, acute cutaneous irritation, or skin sensitization. These results suggested that silica NPs-induced ROS generation was the determinant of cytotoxicity. This study showed that the smaller size (20 nm) of silica NPs had more toxicity than the larger size (100 nm) of silica NPs for NC silica NPs. Moreover, we observed an effect of surface charge in cytotoxicity and ROS generation, by showing that the NC silica NPs (20 nm) had more toxic than the WNC silica NPs (20 nm). These findings suggested that the surface charge of silica NPs might be the important parameter for silica NPs-induced toxicity. Further study is needed to assess the effect of surface modification of nanotoxicity.

There is increasing interest in the therapeutic potential of stem cells because stem cells are promising candidates for the regeneration of tissue and treatment of diseases. Increasing evidence supports, multipotent stem cells may be obtained postnatally in different organs and tissues including bone marrow, synovium, adipose tissue, muscle and dental pulp. To determine a suitable cell source, the stem cells derived from periosteum and bone marrow of jaw bone(mandible) and long bone(tibia) were compared using rabbit models (JPO: periosteum from jaw-bone, JBM: bone marrow from jaw-bone, LPO: periosteum from long-bone, and LBM: bone marrow from long-bone). This study evaluated the proliferation and multilineage differentiation of the cells and clearly showed that expansion ability of JPO was higher than that of bone marrow derived cells. Comparisons of four different stem cells indicated that JPO group is the highest osteogenic potential. Moreover, this study has demonstrated that JPO, JBM and LBM are superior in terms of osteogensis and JPO, LPO and LBM are superior in terms of chondrogensis. Collectively, stem cells derived from jaw bone periosteium revealed highest osteogenic properties with relatively low morbidity with higher availability. Thus, it can be suggested that that periosteum from the jaw bone may be considered as optimal candidate for source of pluripotent stem cells with multi-germline potential with highest expansion ability and osteogenicity.

In spite of widely use of zinc oxide (ZnO) nanoparticles (NPs) in cosmetic industry and in our daily lives, insufficient studies have evaluated the potential of their toxic response. This study was conducted to investigate the potential of cytotoxicity induced by ZnO NPs, especially influences of the surface charge and different particle size. Assessment of potential of skin irritation was estimated using human skin equivalent model (HSEM), and an animal model. And the evaluation of skin phototoxicity was tested by the 3T3 neutral red uptake test. Lastly, the potential of skin sensitization was evaluated by a local lymph node assay (LLNA). The results from this study demonstrated that ZnO NPs are not dermal sensitizers and do not induce skin irritation. But they may produce phototoxicity.

In spite of widely use of zinc oxide (ZnO) nanoparticles (NPs) in cosmetic industry and in our daily lives, there are insufficient data on their potential of skin absorption. This study was conducted to investigate the potential of skin absorption induced by ZnO NPs, especially influences of the surface charge and different particle size. Assessment of potential of skin absorption was estimated using 3D EpiDerm™ model (EPI-200) as human skin equivalent model (HSEM). This study demonstrated no evidence of significant penetration of ZnO NPs into the HSEM after 24 h exposure.

Zinc oxide (ZnO) nanoparticles (NPs) are used in the cosmetic industry in cosmetics and sunscreen. ZnO NPs have been reported to elicit various adverse cellular effects, including cytotoxicity. However, the underlying mechanisms of these adverse effects have not been fully characterized. To investigate the potential of cytotoxicity induced by ZnO NPs, we evaluated cytosolic reactive oxygen species levels in human keratinocyte HaCaT cells treated with ZnO NPs having different surface charges and particle sizes. A short period of treatment (30 min) with 100 nm ZnO NPs resulted in a greater increase of cytosolic ROS levels, compared to treatment with 20 nm ZnO NPs at the same concentration. During a long period of treatment (24 h) with ZnO NPs, intracellular ROS was increased in cells treated with 20 μg/mL 20 nm (+/−) charged ZnO. No significant difference according to differences in surface charge was observed. In addition, total levels of caspase-7 and PARP were decreased by ZnO NPs. These results demonstrated that ZnO NPs could induce ROS mediated apoptosis.

Despite widespread use of silicon dioxide (SiO2) NPs in industry and in our daily lives, no studies so far have evaluated the potential of their skin phototoxicity and sensitization. This study was designed to investigate the potential of phototoxicity and sensitization of SiO2 NPs. Assessment of the potential of skin phototoxicity was carried out using the 3T3 neutral red uptake test, an HSEM, and an animal model. The potential of skin sensitization was evaluated by a non-radioisotope local lymph node assay (non-RI LLNA). Findings from the present study suggest that the HSEM may be a reasonable model system for evaluation of skin phototoxicity of NPs. In addition, our data demonstrate that non-RI LLNA may be a useful method for identification of skin sensitization of NPs. In this study, we showed that SiO2 NPs do not induce phototoxicity or skin sensitization.

Quantum dots (QDs) nanoparticles have potential applications in biomedical research, as imaging and diagnostic agents, because of their fluorescent property. Despite the widespread use of nanoparticles, there are many unknowns in understanding on their nanotoxicities and mechanisms. This study evaluated the effects of Quantum Dots (QDs) on gene expression profiles of human keratinocyte HaCaT cells. Total RNA was prepared from the exposure groups to QDs with diverse physicochemical properties (565-PEG-amine, 565-carboxylic acid, 655-carboxylic acid) in various concentrations, and real-time RT-PCR analysis was performed using human oxidative stress and antioxidant defense array. Our study indicated that antioxidant defense and oxidative stress category, such as nitric oxide synthase 2A (NOS2A), dual specificity phosphatase 1 (DUSP1), dual oxidase (DUOX), 24-dehydrocholesterol reductase (DHCR24), peroxidase in homolog (Drosophila)-like (PXDNL), scavenger receptor class A (SCARA3) and thyroid peroxidase (TPO), were represented by all three QDs exposure groups. Therefore, the up-regulation of these enzymes by QDs could increase the production of reactive oxygen species (ROS). The results of our study showed that QDs contained a potential to produce ROS via metabolic pathways, inducing oxidative stress. The results supported that the mechanism of nanotoxicity could be correlated with active oxygen production, oxidative stress, apoptosis, and antioxidant defense mechanisms.

There is an increasing concern regarding the potential toxicity of nanoparticles (NPs), but little literature is available on its skin toxicity and irritation potential. We investigated whether multi-walled carbon nanotubes (MWCNTs) affect skin irritation using HaCaT cell line, the human skin equivalent model (HSEM), and anin vivo model. We evaluated the cytotoxic effects of MWCNTs on HaCaT cells and the HSEM. To confirm in vitro results, we evaluated the irritation potentials of MWCNTs on rabbit skin. In MTT assay, MWCNTs cytotoxicity depended on the concentration of MWCNTs in HaCaT cells. The HSEM skin irriation experiments revealed that MWCNTs have no irritation potential. These HSEM data are consistent with Draize skin irritation test. MWCNTs did not induce the cutaneous irritation of rabbit skin. We suggest that MWCNTs do not induce any acute cutaneous irritation and the HSEM offers a useful alternative method for evaluating the toxicities of toxicants including NPs.

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1β and interferon-γ levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.