PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes. Toxicol Lett

Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Bygn. 1260, 8000 Aarhus, Denmark.
Toxicology Letters (Impact Factor: 3.26). 08/2009; 190(2):156-62. DOI: 10.1016/j.toxlet.2009.07.009
Source: PubMed


The objective of the present study was to investigate the toxicity of silver nanoparticles (Ag NPs) in vitro. Silver ions (Ag+) have been used in medical treatments for decades whereas Ag NPs have been used in a variety of consumer products within recent years. This study was undertaken to compare the effect of well characterized, PVP-coated Ag NPs (69 nm +/- 3 nm) and Ag+ in a human monocytic cell line (THP-1). Characterization of the Ag NPs was conducted in both stock suspension and cell media with or without serum and antibiotics. By using the flowcytometric annexin V/propidium iodide (PI) assay, both Ag NPs and Ag+ were shown to induce apoptosis and necrosis in THP-1 cells depending on dose and exposure time. Furthermore, the presence of apoptosis could be confirmed by the TUNEL method. A number of studies have implicated the production of reactive oxygen species (ROS) in cytotoxicity mediated by NPs. We used the fluorogenic probe, 2',7'-dichlorofluorescein to assess the levels of intracellular ROS during exposure to Ag NPs and Ag+. A drastic increase in ROS levels could be detected after 6-24h suggesting that oxidative stress is an important mediator of cytotoxicity caused by Ag NPs and Ag+.

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    • "The high sensitivity of U251 cells (compared with normal IMR-90 cells) should be further explored to evaluate the potential use of Ag NPs in cancer therapy (Asha Rani et al. 2009). Similarly, ROS-mediated apoptosis and necrosis were induced in human cancer THP-1 cells by PVP-coated Ag NPs (Foldbjerg et al. 2009). Nec-1 has been reported to inhibit caspase-independent necrotic cell death by inhibiting RIP1 kinase. "
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    ABSTRACT: There has been little focus on the promising ability of metal-based nanoparticles (NPs) to kill cancer cells while sparing normal cells. Many in vitro and in vivo reports suggest that certain metal-based NPs are able to induce apoptosis and autophagy in cancer cells at specific concentrations that are not significantly toxic to non-cancerous cells. Those NPs are thought to exploit the oxidative stress conditions that prevail in cancer cells, which are largely exhausted of antioxidant ability. This review considers the induction of reactive oxygen species (ROS) by metal-based NPs as a mechanism for the specific killing of cancer cells. The article concomitantly provides a comprehensive description of the important pathways and molecules leading to programmed cell death (PCD), which occurs mainly via apoptosis, autophagy, and necroptosis. The PCD pathways are followed as ROS-burdened cancer cells succumb to ROS-generating metal-based NPs. Exploration of nanotechnology interventions in anticancer therapy demands further research into the mechanism of intracellular induction of ROS by metal-based NPs. Furthermore, the induction of ROS by NPs should be strictly controlled if ROS-based therapy is to become a paradigm in cancer therapy.
    Archives of Toxicology 07/2015; DOI:10.1007/s00204-015-1570-1 · 5.98 Impact Factor
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    • "Silver nanoparticles with novel physico-chemical properties could be fabricated from Ag using modern advancements in nanotechnology. Although Ag has strong antibacterial activity, the toxicity of Ag could result in a significant reduction in cell viability and proliferation [7] [8]. Although there are some potential risks of Ag nanoparticles related to cytotoxicity, reports confirmed their applicability as an effective implantable material in reducing probable postoperative infections [8] [9]. "
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    ABSTRACT: Peritendinous adhesions, one of the common complications after tendon injury and subsequent surgery, could be minimized by directly placing a physical barrier between the injured site and the surrounding tissue. We used silver (Ag) nanoparticles embedded in electrospun hyaluronic acid (HA)/polycaprolactone (PCL) nanofibrous membranes (NFMs) (HA/PCL+Ag NFMs) to prevent peritendinous adhesions and bacterial infection after tendon surgery. HA was used for effective lubrication, and Ag provided antibacterial activity. A dual functional anti-adhesion barrier with core-sheath nanofibrous architecture was made from an HA core solution and a photo-reduced silver nitrate/PCL sheath solution. Polycaprolactone NFMs (PCL NFMs), hyaluronic acid/polycaprolactone core-sheath NFMs (HA/PCL NFMs) and HA/PCL+Ag NFMs with comparable fiber diameters and pore sizes were prepared and analyzed. The microporous structure of NFMs is expected to effectively block the penetration of adhesion-forming fibroblasts during tendon healing. The release of Ag from HA/PCL+Ag NFMs plateaued after 4 days, which confirmed the short-term anti-bacterial effect, and this result was verified with agar diffusion tests. In contrast, the release of HA was extended up to 21 days to simulate the lubrication effect offered by HA in the synovial fluid of the tendon sheath. In vitro cell culture experiments revealed that HA/PCL+Ag NFMs exhibited the highest inhibition of fibroblast attachment and proliferation without significant cytotoxicity due to the synergistic effect of Ag and HA. In vivo studies with a rabbit flexor tendon model further confirmed the efficacy of HA/PCL+Ag NFMs in reducing peritendinous adhesion as determined by gross observation, histology, joint range-of-motion, tendon gliding and biomechanical tests. Copyright © 2015. Published by Elsevier Ltd.
    Acta biomaterialia 07/2015; DOI:10.1016/j.actbio.2015.07.041 · 6.03 Impact Factor
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    • "They are also used as filtering agents in humidifiers and water purification treatments [7]. AgNPs are highly chemically reactive due to their small size and high surface area, which produces a great amount of reactive oxygen species (ROS) [8]. ROS and free radical production cause oxidative stress, inflammation, and protein , DNA, and membrane damage. "
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    ABSTRACT: Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb) protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.
    Toxicology Reports 05/2015; 411. DOI:10.1016/j.toxrep.2015.05.005
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