Krupa Kansara

TiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cells

TiO2 nanoparticles (NPs) have the second highest global annual production (∼3000 tons) among the metal‐containing NPs. These NPs are used as photocatalysts for bacterial disinfection, and in various other consumer products including sunscreen, food packaging, therapeutics, biosensors, surface cleaning agents, and others. Humans are exposed to these NPs during synthesis (laboratory), manufacture (industry), and use (consumer products, devices, medicines, etc.), as well as through environmental exposures (disposal). Hence, there is great concern regarding the health effects caused by exposure to NPs and, in particular, to TiO2 NPs. In the present study, the genotoxic potential of TiO2 NPs in A549 cells was examined, focusing on their potential to induce ROS, different types of DNA damage, and cell cycle arrest. We show that TiO2 NPs can induce DNA damage and a corresponding increase in micronucleus frequency, as evident from the comet and cytokinesis‐block micronucleus assays. We demonstrate that DNA damage may be attributed to increased oxidative stress and ROS generation. Furthermore, genomic and proteomic analyses showed increased expression of ATM, P53, and CdC‐2 and decreased expression of ATR, H2AX, and Cyclin B1 in A549 cells, suggesting induction of DNA double strand breaks. The occurrence of double strand breaks was correlated with cell cycle arrest in G2/M phase. Overall, the results indicate the potential for genotoxicity following exposure to these TiO2 NPs, suggesting that use should be carefully monitored. Environ. Mol. Mutagen. 56:204–217, 2015.

Cell cycle dependent cellular uptake of zinc oxide nanoparticles in human epidermal cells

Metal oxide nanoparticles (NPs), including zinc oxide (ZnO) NPs have shown success for use as vehicles for drug delivery and targeting gene delivery in many diseases like cancer. Current anticancer chemotherapeutics fail to effectively differentiate between cancerous and normal cells. There is an urgent need to develop novel drug delivery system that can better target cancer cells while sparing normal cells and tissues. Particularly, ZnO NPs exhibit a high degree of cancer cell selectivity and induce cell death, oxidative stress, interference with the cell cycle progression and genotoxicity in cancerous cells. In this scenario, effective cellular uptake of NP seems to be crucial, which is shown to be affected by cell cycle progression. In the present study, the cytotoxic potential of ZnO NPs and the effect of different cell cycle phases on the uptake of ZnO NPs were examined in A431 cells. It is shown that the ZnO NPs led to cell death and reactive oxygen species generation and were able to induce cell cycle arrest in S and G2/M phase with the higher uptake in G2/M phase compared with other phases.

TiO2 nanoparticles induce cytotoxicity and genotoxicity in human alveolar cells.

Background Engineered nanoparticles (ENPs) such as TiO2 are widely used in products such as cosmetics, clothing, food packaging, drug delivery systems, etc. due to their unique physicochemical properties. This has increased the liklihood of ENP exposure in humans. As the ENPs are having small size and high diffusion coefficient, they can migrate rapidly in the air. Therefore, inhalation is considered to be the primary route of exposure to such ENPs. Hence, in the present study an attempt was made to assess the potential toxicological effects of TiO2 NPs in human alveolar cell line (A549).

Cytotoxicity assessment of ZnO nanoparticles on human epidermal cells

Background Nanotechnology is growing rapidly worldwide and engineered nanoparticles have found tremendous applications in consumer and industrial products. Metal oxide nanoparticles (NPs), especially zinc oxide (ZnO), are widely used in cosmetics, catalysis, electronics, biosensors, medicine, paints, food packaging and imaging. As, the ZnO NPs have major application in cosmetics, their exposure will mainly be through the skin, which is the largest organ of the body and could serve as an important portal route for entry. Therefore, the present study was carried out to assess the cytotoxicity of ZnO NPs on human epidermal cells (A431).

Cellular internalization and antioxidant activity of cerium oxide nanoparticles in human monocytic leukemia cells

Overproduction of free radicals contributes to oxidative stress and inflammation leading to various disease conditions. Cerium oxide nanoparticles (nanoceria) have been shown to scavenge free radicals and have the potential for being used as a therapeutic agent in disease conditions. Therefore, in the present study, human monocytic leukemia cells (THP-1) were used as a model to evaluate the uptake and free radical scavenging activity of nanoceria. Our data showed a significant (P<0.05) increase in the internalization of nanoceria in a concentration-dependent (10–100 µg/mL) manner in THP-1 cells. Although no cytotoxicity was observed at these concentrations, nanoceria significantly (P<0.05) reduced the amount of reactive oxygen species. This was evident by a significant (P<0.05) decrease in the 2,7-dichlorofluorescein diacetate fluorescence observed in flow cytometry and fluorescence microscopy. The present study shows that nanoceria have therapeutic potential in diseases such as cancer.

Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle

Over the last decade, there has been growing interest in developing novel nanoparticles (NPs) for biomedical applications. A safe-by-design approach was used in this study to synthesize biocompatible iron oxide NPs. The size of the particles obtained was ~100 nm. Although these NPs were significantly (P<0.05) internalized in MCF-7 (human breast adenocarcinoma cell line) cells, no adverse effect was observed in the cells as assessed by cytotoxicity assays (neutral red uptake and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and cell cycle analysis. Our data demonstrate the potential of iron oxide NPs as a biocompatible carrier for targeted drug delivery.

Curcumin Ag nanoconjugates for improved therapeutic effects in cancer

Curcumin has a broad spectrum of pharmacological activities, one of them is anticancer activity that is mediated through multiple mechanisms. The major disadvantage associated with the use of curcumin is its low bioavailability due to its poor aqueous solubility. Nanoformulations of curcumin provide an effective solution for this problem. In this study, we have synthesized curcumin Ag nanoconjugates and evaluated their anticancer potential.

DNA Damage, Repair, and Maintenance of Telomere Length: Role of Nutritional Supplements

Abstract DNA damage is a physiological phenomenon, which modifies the chemical structure of DNA. DNA damages can occur naturally or may be induced, and DNA molecule is extremely vulnerable to damage and injury from both internal and external sources. Naturally occurring DNA damages result mainly from metabolic processes, mostly due to the generation of reactive oxygen species. To counter the DNA damage, cells have evolved a plethora of DNA repair pathways, which perform the function of surveillance and maintenance of DNA integrity. Telomeres are repetitive DNA sequences present at the end of the chromosomes and functions to protect the ends from deletions as well as fusion with other chromosomes. There is a large body of literature indicating the role of nutritional supplements in DNA repair and maintenance of telomere length. The objective of this chapter is to provide a comprehensive account of the role of different nutritional supplements in DNA repair and maintenance of telomere length.DNA damage is a physiological phenomenon, which modifies the chemical structure of DNA. DNA damages can occur naturally or may be induced, and DNA molecule is extremely vulnerable to damage and injury from both internal and external sources. Naturally occurring DNA damages result mainly from metabolic processes, mostly due to the generation of reactive oxygen species. To counter the DNA damage, cells have evolved a plethora of DNA repair pathways, which perform the function of surveillance and maintenance of DNA integrity. Telomeres are repetitive DNA sequences present at the end of the chromosomes and functions to protect the ends from deletions as well as fusion with other chromosomes. There is a large body of literature indicating the role of nutritional supplements in DNA repair and maintenance of telomere length. The objective of this chapter is to provide a comprehensive account of the role of different nutritional supplements in DNA repair and maintenance of telomere length.

Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle [Corrigendum]

[This corrects the article on p. 79 in vol. 13, PMID: 29593401.].

Formulation of vitamin D encapsulated cinnamon oil nanoemulsion: Its potential anti-cancerous activity in human alveolar carcinoma cells

Cinnamon oil is used for medicinal purpose since ancient time because of its antioxidant activity. Oil-in-water nanoemulsion (NE) of cinnamon oil was formulated using cinnamon oil, nonionic surfactant Tween 80 and water by ultrasonication technique. Phase diagram was constructed to investigate the influence of oil, water and surfactant concentration. Vitamin D encapsulated cinnamon oil NE was fabricated by wash out method followed by ultrasonication in similar fashion. The hydrodynamic size of cinnamon oil NE and vitamin D encapsulated cinnamon oil NE was observed as 40.52 and 48.96 nm in complete DMEM F12 media respectively. We focused on the cytotoxic and genotoxic responses of NEs in A549 cells in concentration dependent manner. We observed that both NEs induce DNA damage along with corresponding increase in micronucleus frequency that is evident from the comet and CBMN assay. Both the NEs arrested the cell cycle progression in G0/G1 phase, showed increased expression of Bax, capase-3 and caspase-9 and decrease expression of BcL2 proteins along with significant (p < 0.05) increase in apoptotic cell population and loss of mitochondrial membrane potential. NEs were also evaluated for bactericidal efficacy against E. coli. Thus, both NEs have cytotoxic, genotoxic and antibacterial potential and hence can also be used in food industry with cinnamon oil as carrier for lipophilic nutraceutical like vitamin D.