Cytotoxicity mechanism of non-viral carriers polyethylenimine and poly-l-lysine using real time high-content cellular assay

Cationic polymers polyethylenimine (PEI) and poly-l-lysine (PLL) used as non-viral gene/drug delivery vehicles, showed high cytotoxicity but their molecular mechanisms of toxicity have been inadequately understood. Therefore, we tried to investigate the toxicity pathway triggered by these polymers through a high-content cellular imaging technique. The results revealed that PEI induced apoptosis via an intrinsic pathway, whereas PLL showed cytotoxicity through both intrinsic and extrinsic caspase cascade. Both PEI and PLL provide different apoptotic activities on HepG2 cells depending on their molecular weight. The degree of apoptosis of PEI also depends on its structure. The branched PEI showed higher cytotoxicity than linear PEI. This observation was verified through Annexin V-FITC/PI assay and real-time high-content monitoring of cytosolic calcium, mitochondrial membrane disruption, and caspase-3 activation methods. The study therefore provides important implications on the molecular mechanisms of PEI and PLL induced cytotoxicity.     

Mortality response of folate receptor-activated,PEG–functionalized TiO2 nanoparticles for doxorubicin loading with and without ultraviolet irradiation

TiO₂ nanoparticles (NPs) were synthesized by hydrothermal assisted sol–gel technique. In the next step, as-synthesized NPs were modified by poly ethylene glycol (PEG). Then, folic acid (FA) was conjugated to TiO₂–PEG. Finally, Doxorubicin (Dox) as an anticancer drug was loaded on as-prepared TiO₂–PEG–FA nanocarrier. The optimization of TiO₂ and FA concentration and the influence of ultraviolet (UV) irradiation on photocatalytic activity of nanocarrier and Dox loaded carrier were assessed by utilizing the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT)-assay method.     

Zinc selenide nanoparticles (ZnSe-NPs): Green synthesis and investigation of their cytotoxicity effects

Mono-dispersed crystalline Zinc selenide nanoparticles (ZnSe-NPs) have been synthesized at ambient temperature conditions via a “green” chemistry method. The nanoparticles were characterized by Transmission electron microscopy (TEM) and UV–vis spectrophotometry. In vitro cytotoxicity studies on Neuro2A and HeLa cell lines illustrated a dose dependent toxicity with non-toxic effect of ZnSe-NPs up to a concentration of 3.9 and 7.8 µg/mL, respectively. The influencing reaction time was also investigated, and the possible formation mechanism was also proposed. The suggested method is facile, green, easy, and it can be employed to large-scale fabrication.     

Impact of physicochemical properties of cerium oxide nanoparticles on their toxicity effects

The advancing production and application of cerium oxide nanoparticles (CeO₂-NPs) in recent years have raised scientists concern about their toxicity. Numerous investigations have been performed to study the toxicity of CeO₂-NPs although their results are sometimes contradictory. In this review, we display the most important factors that are effective in CeO₂-NPs toxicity. The studies are classified based on the target that is selected for toxicity assessment (cytotoxicity, respiratory toxicity, hepatotoxicity, neurotoxicity, dermal toxicity, phytotoxicity, and environmental toxicity). Various representative examples are presented in each class. It seems to be difficult to achieve a comprehensive view and a deterministic conclusion since several parameters are involved in interpreting the results. In order to reach repeatable and comparable results, it is necessary to design a standard protocol to study the toxicity of CeO₂-NPs. Physicochemical properties of nanoparticles, experiment set up, and toxicity assessment methods are some parameters that should be considered in this standardization.     

Hemocompatibility,cytotoxicity, and genotoxicity of poly(methylmethacrylate)/nanohydroxyapatite nanocomposites synthesized by melt blending method

The aim of this study was to show the hemocompatibility, cytotoxicity, and genotoxicity of nanocomposites that were synthesized with different molecular weights of poly(methyl methacrylate) (PMMA) and different concentrations of nanohydroxyapatite (nHAp). Different techniques to characterize the nanocomposites were used. The cytotoxicity and genotoxic effects of the polymers and nanocomposites on human lymphocytes were determined by acid phosphatase assay, viability test, and comet assay. Moreover, hemocompatibility test was performed. It was found that all of the PMMA/nHAp nanocomposites are highly hemocompatible and biocompatible, none of the nanocomposites showed a cytotoxic effect, and nHAp addition decreased the genotoxicity.     

Genotoxicity of silver nanoparticles in Allium cepa

Potential health and environmental effects of nanoparticles need to be thoroughly assessed before their widespread commercialization. Though there are few studies on cytotoxicity of nanoparticles on mammalian and human cell lines, there are hardly any reports on genotoxic and cytotoxic behavior of nanoparticles in plant cells. This study aims to investigate cytotoxic and genotoxic impacts of silver nanoparticles using root tip cells of Allium cepa as an indicator organism. A.cepa root tip cells were treated with four different concentrations (25, 20, 75, and 100 ppm) of engineered silver nanoparticles (below 100 nm size) dispersion, to study endpoints like mitotic index, distribution of cells in mitotic phases, different types of chromosomal aberrations, disturbed metaphase, sticky chromosome, cell wall disintegration, and breaks. For each concentration five sets of microscopic observations were carried out. No chromosomal aberration was observed in the control (untreated onion root tips) and the mitotic index (MI) value was 60.3%. With increasing concentration of the nanoparticles decrease in the mitotic index was noticed (60.30% to 27.62%). The different cytological effects including the chromosomal aberrations were studied in detail for the treated cells as well as control. We infer from this study that silver nanoparticles could penetrate plant system and may impair stages of cell division causing chromatin bridge, stickiness, disturbed metaphase, multiple chromosomal breaks and cell disintegration. The findings also suggest that plants as an important component of the ecosystems need to be included when evaluating the overall toxicological impact of the nanoparticles in the environment.     

Chemical composition, in vitro cytotoxic and antioxidant activities of the essential oil and major constituents of Cymbopogon jawarancusa (Kashmir)

The chemical composition of the hydrodistillate of aerial parts of Cymbopogon jawarancusa, a natural grass considered as major forage for animal nutrition, used in food because of the presence of sufficient concentration of minerals like calcium and potassium was analysed by capillary GC–FID, GC–MS and ¹³C NMR. Seventeen constituents representing 97.8% of the total oil with piperitone (58.6%) and elemol (18.6%) as major constituents were identified. In vitro cytotoxicity of the oil and its constituents on human cancer cell lines THP-1 (leukemia), A-549 (lung), HEP-2 (liver) and IGR-OV-1 (ovary) was evaluated by Sulphorhodamine-B assay. The oil was found to be more potent than its components against cancer cell lines tested with IC₅₀ of 6.5 μg/ml (THP-1), 6.3 μg/ml (A-549), 7.2 μg/ml (HEP-2) and 34.4 μg/ml (IGR-OV-1). Antioxidant activity of oil and its constituents was evaluated by DPPH assay. In conclusion, the results demonstrate potent cytotoxic and antioxidant effects of oil, and its components like piperitone, α-pinene, β-caryophyllene and β-elemene.     

In vitro corrosion and cytotoxicity on microcrystalline, nanocrystalline and amorphous NiTi alloy fabricated by high pressure torsion

Bulk nanocrystalline and amorphous Ni50.2Ti49.8 alloy samples were successfully prepared from commercial microcrystalline Ni50.2Ti49.8 alloy discs by high pressure torsion (HPT) technique. Then their corrosion resistance, surface wettability and cytotoxicity were further studied from the viewpoint of biomaterials. In both Hank's solution and artificial saliva, bulk nanocrystalline and amorphous Ni50.2Ti49.8 alloys showed significantly higher pitting corrosion potentials than that of microcrystalline Ni50.2Ti49.8 alloy. Meanwhile, the amount of Ni ion release after immersion in Hank's solution was minor, far below the threatening threshold of daily diet. Murine fibroblast and osteoblast cell lines were indirectly co-cultured with experimental sample extracts, indicating no cytotoxicity. Amongst all samples, the nanocrystalline Ni50.2Ti49.8 shows promising as best biomaterial candidate for its good combination of mechanical property, corrosion resistance and cytocompatibility.     

Isolation of a hydroxytyrosol-rich extract from olive leaves (<Emphasis Type="Italic">Olea Europaea</Emphasis> L.) and evaluation of its antioxidant properties and bioactivity

In this research, a phenol extract of high hydroxytyrosol (OLPE) content was obtained from olive leaves (Olea europaea L.), and subsequently tested under different contexts. The method used to obtain the OLPE basically involved two steps: the use of strongly-acid aqueous steam, generated from 10% HCl (v/v) at 100°C, to directly hydrolyse the native complex phenols from integral olive leaves, and OLPE recovery by liquid–liquid extraction with ethyl acetate. Hydrolysis time was 1 h. Finally, the dried extract was dissolved in distilled water. The OLPE total phenols were determined by Folin–Ciocalteu’s method and by HPLC analysis. Hydroxytyrosol was about 92% of the total phenols present in OLPE, and the yield was about 0.2% on fresh leaves. OLPE showed antioxidant effects on different food lipids and did not inhibit lactic acid bacteria growth; however, it showed cytotoxicity on NIH/3T3 fibroblasts and human umbilical vein endothelial cells at concentrations higher than 0.32 mM (as hydroxytyrosol).     

乙双吗啉对人肺腺癌细胞系SPC-A-1的辐射增敏特性

乙双吗啉(AT_(1727))是我国自行合成的派嗪二酮类抗肿瘤药物,它的放射增敏性近年来引起了各方面的关注。本文以人肺腺癌细胞系SPC—A—1为材料,用体外细胞集落形成法研究了乙双吗啉在乏氧条件下的辐射增敏性,结果表明当药物浓度为0.15m mol/L时,增敏比为1.33。对现有资料进行分析,提出乙双吗啉可能以某种方式作用于乏氧的肿瘤细胞。