Investigation of cytotoxic effects of different ZnO nanostructures on living cancer cells (original) (raw)
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ZnO Nanoparticles: A Promising Anticancer Agent
Nanobiomedicine, 2016
Nanoparticles, with their selective targeting capabilities and superior efficacy, are becoming increasingly important in modern cancer therapy and starting to overshadow traditional cancer therapies such as chemotherapy, radiation and surgery. ZnO nanoparticles, with their unique properties such as biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may be a promising anticancer agent. Zinc, as one of the major trace elements of the human body and co-factor of more than 300 mammalian enzymes, plays an important role in maintaining crucial cellular processes including oxidative stress, DNA replication, DNA repair, cell cycle progression and apoptosis. Thus, it is evident that an alteration in zinc levels in cancer cells can cause a deleterious effect. Research has shown that low zinc concentration in cells leads to the initiation and progression of cancer and high zinc concentration shows toxic effects. Zinc-mediated protein activity disequilibrium and oxidative stress through reactive oxygen species (ROS) may be the probable mechanism of this cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer cells due to enhanced permeability and retention (EPR) effect and electrostatic interaction and selective cytotoxicity due to increased ROS present in cancer cells show that ZnO nanoparticles can selectively target and kill cancer cells, making them a promising anticancer agent.
Cytotoxic Effects of Biosynthesized Zinc Oxide Nanoparticles on Murine Cell Lines
The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 𝜇g/mL (4T1), 17.45 ± 1.1 𝜇g/mL (CRL-1451), 11.75 ± 0.8 𝜇g/mL (CT-26), and 5.6 ± 0.55 𝜇g/mL (WEHI-3B), respectively. On the other hand, ZnONPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 𝜇g/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death inWEHI-3 cells.Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.
ANTI CANCER ACTIVITY OF ZnO NANOPARTICLES on MCF7 (BREAST CANCER CELL) AND A549 (LUNG CANCER CELL
ZnO nanoparticles have been proved to be promising in cancer treatment, including the tumor cells destruction with minimal damage to the healthy cells. In the present study highly pure ZnO nano particles with a narrow size distribution of 16-19 nm were prepared by the simple DMC (Dry Mechano-Chemical) method in the lab. The anticancer activity on MCF7 (Breast cancer cell) and A549 (Lung Cancer cell) were determined by the MTT (Methylthiazolydiphenyl-tetrazolium bromide) assay. A549 and MCF-7 cells were exposed to ZnO-NPs and it exhibited 50% reduction at a very low concentration 31.2 μg/ml. Thus, the reduction in cell viability with NPs induces cytotoxicity in cancerous cells. There is a size dependent effectiveness of ZnO nanoparticles in the removal of cancer cells and also a positive correlation with reduced toxicity.
Selective cytotoxic effect of ZnO nanoparticles on glioma cells
Nano Research, 2009
In this study we examined the cytotoxic effect of ZnO nanoparticles on various human cancer and normal cells. We found that the ZnO nanoparticles exerted a cytotoxic effect on the human glioma cell lines A172, U87, LNZ308, LN18, and LN229, whereas no cytotoxic effect was observed on normal human astrocytes. Similarly, the ZnO nanoparticles induced cell death in breast and prostate cancer cell lines while no major effect was observed in the respective normal breast and prostate cell lines. Using the fl uorescent dye 2,7-dichlorofl uorescein diacetate, we found that treatment of the glioma cells with ZnO nanoparticles induced a large increase in the generation of reactive oxygen species (ROS) and treatment of the cells with N-acetyl cysteine decreased the cytotoxic effect of the ZnO nanoparticles. In contrast, a smaller effect on ROS generation was observed in the normal astrocytes. These results suggest that ZnO nanoparticles may be employed as a selective cytotoxic agent for the eradication of cancer cells.
Toxicological mode of action of ZnO nanoparticles: Impact on immune cells
Molecular immunology, 2015
The use of nanoscale materials is growing exponentially as concerns rise about the human hazards to it. It is assumed that living beings are coevolved with nanoparticles ever since the origin of life on earth and therefore, they must have developed the defense and toxicity mitigating mechanisms for nanoparticles. Although having peculiar properties these new materials also present new health risks upon interacting with biological systems. Zinc oxide is the most widely used nanoparticles among various nanomaterials. Recently, these nanoparticles have been shown to specifically kill cancerous cells; therefore, it is believed that these nanoparticles may be used as an alternative anti-tumor agent. However, it is also known that these nanoparticles pose several deleterious effects to living beings. It is therefore critical to understand the nature and origin of the toxicity imposed by these nanomaterials. Keeping these points in mind the present review provides updated information on various aspects of toxicities induced by these engineered nanoparticles.
Colloids and Surfaces B: Biointerfaces, 2014
Liver and breast cancer are the most traumatic diseases because they affect the major organs of the body. Nanomedicine recently emerged as a better option for the treatment of these deadly diseases. As a result, many nanoparticles have been used to treat cancer cell lines. Of the various nanoparticles, zinc oxide exhibits biocompatibility. Therefore, the aim of the present study was to investigate the activity of zinc oxide nanoparticles (ZnO-NPs) against HepG2 and MCF-7 cells. The NPs (∼13 ± 2 nm) were prepared via a non-protonated chemical route and were well-characterized through standard techniques. The study showed that treatment with NPs is notably effective against the proliferation of HepG2 and MCF-7 cancer cells in a dose-dependent manner. The MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, a tetrazole) assays revealed the concentration-dependent cytotoxic effects of NPs in range of 2.5-100 g/ml. HepG2 and MCF-7 cells were exposed to ZnO-NPs and exhibited a significant reduction in their cell viability (95% and 96%; p < 0.05) in response to a very low concentration (25 g/ml) of the ZnO-NPs; this finding was confirmed with FACS (fluorescence-activated cell sorting) data. The reduction in cell viability in response to NP treatment induces cytotoxicity in the cultured cells. The quantitative RT-PCR (real-time polymerase chain reaction) results demonstrate that the exposure of HepG2 cells to ZnO-NPs results in significant upregulation of the mRNA expression level of Bax, p53, and caspase-3 and the down regulation of the anti-apoptotic gene Bcl-2. The NPs were also tested against five pathogenic bacteria through the disk diffusion method, and their antibacterial activities were compared with that of ZnO salt. (R. Wahab). diagnostics, and therapeutics because chemotherapy, radiation, and surgery were the old techniques used to reduce cancers [1-10]. Of the wide range of applications of nanobiotechnology, it is widely applied to reduce cancers with the use of inexpensive inorganic nano-scale materials. Nanomaterials, which have very small diameter (∼30 nm), exhibit unique physicochemical characteristic due to their size; these include a high surface area, low cost, enhanced reactivity, ability to easily enter cells, and ability to affect various types of biological systems . It is known that cancer is a heterogeneous and complex disease that occurs when the normal cell proliferation controls are lost. The positive/normal cells change into cancer cells through three distinct phases, i.e., initiation, promotion, and progression. Several reports have reported the toxicity of nanostructures, which kill human cancerous cells and are very useful for protection against cancers . Of the various types of cancers, hepatocellular carcinoma is the fourth most common malignant tumour in the world . The incidence http://dx.
Journal of Biological …, 2010
ZnO nanostructures of diverse shape were grown via a solution process with different precursors and conditions. Morphological investigation of the nanostructures was carried out using field emission scanning electron microscopy and transmission microscopy observations and revealed that the nanostructures exhibit a wurtzite phase with an ideal lattice fringe distance of approximately 0.52 nm. The powder crystallinity was examined via X-ray diffraction spectroscopy. Screening results from anticancer studies of the effects on human brain tumor U87, cervical cancer HeLa, and normal HEK cells of ZnO nanostructures of diverse shape were obtained and indicate promising activity that varies with changes in the structure and the size of the particles. Treatment-induced cell death [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and survival assay], growth inhibition, cytogenetic damage (formation of micronuclei), and apoptosis were studied as parameters for the cellular response. Treatment with nanostructures enhanced growth inhibition and cell death in a concentration-dependent manner in both U87 and HeLa cell lines. At higher concentrations (above 15.6 lg/ml) the cytotoxic effects of the nanoparticles were highly synergistic and mainly mediated through apoptosis, implying the possible interactions of lesions caused by the agents. The enhanced cell death due to nanoparticles was accompanied by a significant increase (2-3 fold at 31.25 lg/ml) in the formation of micronuclei in U87 cells. The increase in the formation of micronuclei observed after treatment indicates that these structures may interfere with the rejoining of DNA strand breaks. Among all the nanostructures, nanoparticles and sheets exhibited potent activity against both HeLa and U87 cells. However, despite potent in vitro activity, all nanostructures exhibited diminished cytotoxicity against normal human HEK cells at all effective concentrations.
Zinc Oxide Nanoparticles as Potential Novel Anticancer Therapies
2011
Several fellow members of my lab, past and present, are deserving of thanks, including Ashley Masterson and Dr. John Rasmussen for their suggestions, help in day-to day lab functions, and, importantly, their camaraderie. Special thanks must go to Panagiota Louka, for her red blood cell viability data in Figure 3.2A and to Ezequiel Martinez, for his data on erythroleukemia cell viability in Figure 3.2B. I owe to Cory Hanley my deepest gratitude for countless contributions to this work. She contributed authorship to Chapter 2 of this thesis, as well as the primary T and B cell data in Figures 2.1, 2.3, 2.4, and 2.6A, and spent countless hours training me and assisting with blood draws and T cell isolations. Importantly, her familiarity with my thesis allowed her to be a sounding board for result interpretation, frustrations, new ideas, and to be optimally effective in providing suggestions to improve experimental design. In Cory, I also found a lifelong friend, for which I am truly grateful. I give my sincerest thanks to all those mentioned here, for their help with my thesis, and for their part in making my graduate school experience a happy one. viii ABSTRACT Nanoparticles (NP) are increasingly being recognized for their utility in the field of medicine, including use as drug carriers and imaging tools. We demonstrated that ZnO NP preferentially kill cancerous cells of the T cell lineage, and extended this research to evaluate other cells types, including normal and malignant B cells, and normal and malignant breast and prostate epithelial cells. Preferential ZnO nanoparticle cytotoxicity occurred for multiple types of cancer cells, but was most pronounced for non-adherent cells of hematopoietic lineage. Normal T and B lymphocytes showed the greatest resistance to NP toxicity, followed by normal breast epithelial cells, and appeared to be closely tied to cellular proliferative potential. Reactive oxygen species generation contributed, at least in part, towards cancer cell selectivity with greater levels of reactive oxygen species being induced in cancerous cells compared to normal cell counterparts. The extracellular dissolution of ZnO NP did not appear to appreciably contribute to the toxicity mechanism, and endocytosis of nanoparticles appeared to be required for toxicity. Particle charge was found to have an effect on toxicity, with more cationic nanoparticles having a greater toxicity than neutral/anionic particles, and may be an important factor in future studies aimed at improving cancer cell selectivity. Overall, these findings suggest that ZnO nanoparticles may have utility in anticancer regimens aimed at hematological malignancies. ix TABLE OF CONTENTS
2016
ZnO NPs (zinc oxide nanoparticles) has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species) production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.