Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
Nano...
Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
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Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
Nano...
Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
not ...
Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
Rele...
Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
Cert...
Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
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Name: Adwait Suratkar; UID: 1213672
Department of Earth, Environmental Science and Geography
University of Birmingham
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Nanoparticles and production of reactive oxygen species

Published on: Mar 3, 2016
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Transcripts - Nanoparticles and production of reactive oxygen species

  • 1. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Nanoparticles and production of reactive oxygen species (ROS): for how long can we deny this truth? “Oxygen: In one form its gives life... in another it takes” – Adwait P.Suratkar Section. 1 Abstract: Nanotechnology has certainly been one of the most promising fields of research and development. If you look at it from one angle, nanotechnology has myriads of applications, ranging from health care and cosmetic products, medical diagnostics; as coating on surfaces; nanoparticles being used in ceramics and paints which are also a major part of textile industry; they are also being used as anti-microbial agents. The dark side of nanotechnology is its toxic effects not only on humans, but on other organisms living in the environment. In this article we will look at how these nanoparticles end up in cells and how they play a critical role in formation of reactive oxygen species, which eventually decide the fate of the cell. Oxygen the destroyer: Oxygen is biologically one of the most important molecule, but also a molecule that is capable of creating havoc inside a cell in its nascent state or reactive state. Molecular oxygen has two unpaired electrons in its outer most shell, with same spin in same direction; when these electrons are excited by a reacting species, they can produce a molecule called singlet oxygen (1 O2) which is a powerful oxidant (Klaus Apel 2004) that is capable of breaking strong chemical bonds. This reaction usually occurs in the presence of ultra- violet (UV) light, and can also be initiated in the presence of ionizing radiation. Collectively the many different forms of this reactive oxygen are called as reactive oxygen species (ROS). In this section we will be looking at the different forms of reactive oxygen that is produced and released inside a cell. But before that it is important to understand why reactive oxygen species is produced inside a cell or a body, there are two important reasons for this:
  • 2. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Two combat with invading micro-organisms, pathogens and viruses. In human body, macrophages and other lymphocytes are known to use ROS as a mechanism to destroy pathogens. Reactive oxygen species is also produced during the terminal stages of electron transport chain and oxidative phosphorylation. Reactive oxygen species are also encountered at the cell membrane (in the form of an incoming signal). There are also external factors because of which ROS is produced. This article will enlighten you about the possible ROS production by nanoparticles. Reactive oxygen species (ROS): This is a highly reactive species of molecular oxygen produced by the cell during the metabolism of oxygen. They come in various forms (superoxide, hydrogen peroxide, singlet oxygen, Hypochlorous acid); Hydroxyl radicals (OH- and OH+ ) are the most reactive form of oxygen in the biological system, they have a very short half life but can cause serious damage to biological material, they are produced as a result of Fenton reaction. Superoxide anion (O2- ) is a negatively charged but highly destructive species of oxygen when it reduced by electrons, production of this species occurs at the Complex I (NADH: ubiquinone oxidoreductase) of mitochondria (Turrens, J. F. 2003) Hydrogen peroxide is a by product of superoxide reduction. Hydrogen peroxide is the last of the ROS; on further reduction water molecules are produced. What happens to all the ROS produced? Every cell has enzymes and antioxidants present in it to combat and maintain a balance (in terms of concentration) of the reactive oxygen species. Some of the antioxidant enzyme include; i. Superoxide dismutase (SOD), ii. Catalase; (ii) Glutathione peroxidase (GPx); (iii) Cu-Zn Dismutase; there are also certain antioxidant that scavenge on the ROS; they include, (i) Vitamin C; (ii) Vitamin E; (iii) melatonin, etc. The ROS produced in the cells oxidizes mainly the genetic material, causes lipid peroxidation, oxidative stress; overall a lot of cell damage.
  • 3. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Nanoparticles: These tiny particle are have amazing applications and but some of them are relatively new to science and very little is known about its supramolecular chemistry. According to the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) and the Joint Research Centre (JRC), a nanoparticle is defined as "a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm – 100 nm." Nature of nanoparticle plays a critical role: Nanoparticles come in various shapes (triangles, rods, cones, wires), sizes and can be synthesized from various elements. Usually the properties of nanoparticles are tailored to suit the application. There are also intrinsic properties of nanoparticles (novel to a particular class of nanoparticles); they play a critical role while evaluating the toxicity and the behavior of nanoparticles a point of bio-contact (Andre Nel 2009). Semiconductor nanoparticles (Quantum dots) are highly toxic especially cadmium nanoparticles (Jasmina Lovri 2005), as they are soluble in nature and release toxic ions that can be produce reactive oxygen species. The size, shape and the capping agent and the coating on the surface of the nanoparticle (polymer coating, or a biocompatible coating) play a critical role. Semiconductor nanoparticles produce ROS by the production of electron hole pairs that are highly reactive in nature, thereby oxidizing or reducing biomolecules (proteins, enzymes) to produce ROS. Also it is important to note if the nanoparticle is hydrophobic or hydrophilic in nature, certain nanocrystals do not have any coating at there surface, this can make them highly toxic, Rutile and anatase (TiO2)13 nanoparticles are a good example for this, even uncapped silver nanoparticles (1-10nm) that expose the <111> crystal face are possible ROS generators (mélanie auffan 2009). Carbon nanotubes7 are a class of carbon nanoparticles that are toxic because they are insoluble in nature. They get accumulated in the body (especially lungs), they are
  • 4. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham not engulfed by the phagocytes (indirect mechanism of ROS production) because of their size and ―tube‖ like shape. Generation of reactive oxygen species by nanoparticles Fenton chemistry: This occurs in case of very fine iron nanoparticles1 (due to a very large surface area). The already formed hydrogen peroxide inside the cell is converted into hydroxyl radical (OH- ) and (OH+ ), these are as mentioned earlier the most reactive intermediates of ROS. This would further lead to oxidative stress and cell damage. There need a further investigation though if this effect is enhanced by the ―nano‖ of iron particles, (more ions are released in a ―nano‖ then in the bulk.). This phenomenon is also shown by TiO2 nanoparticles (Auffam 2009) (rutile and anatase), but the difference in the case of TiO2 nanoparticles is that they require UV excitation or absorption of light. Figure 1: Reference: Mélanie Auffan, Nature nanotechnology Vol 4 October 2009 The figure explains the relation of size and the novel ―nano‖ properties associated with it. There are also many reactions occurring at the surface of a nanoparticle, ROS production being one of them.
  • 5. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Release of toxic ions can produce ROS: ZnO2 (Anat Lipovsky 2011); chromium (S. J. Stohs 1995) and AgNPs (silver nanoparticles) release toxic ions. This release occurs by reduction or oxidation of nanoparticles inside the body or a cell in individual. Interaction with Mitochondria: The structure, shape and dimensions of mitochondria play a critical in nanoparticle interaction, accumulation and generation of ROS. Referring to figure 2 it is important to note that any nanoparticles with diameter < 14 nm will easily cross the outer membrane of mitochondria and accumulate in the mitochondria. But nanoparticles within the diameter range of 16 to 30 nm will puncture into the mitochondria and can block important pathways like oxidative phosphorylation, electron transport chain and lipid metabolism (due to their large size in comparison to the dimensions of mitochondria), this can stress the mitochondria, disrupt mitochondrial function, a collective effect is oxidative damage, and production and accumulation of ROS. Certain mitochondria have a high percentage of cristae (liver mitochondria); Figure 2: Terrence G. Frey, Carmen A. Mannella; Elsevier Science TIBS 25 – JULY 2000, PII: S0968-0004(00)01609-1. This is a 3D tomogram of mitochondria, showing the dimensions of the organelle, a delicate organelle like mitochondria is an easy target of nanoparticles. Also seen in this figure is Endoplasmic reticulum ( ), responsible for lipid shuttling from & to mitochondria.
  • 6. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Certain mitochondria have a high percentage of cristae (liver mitochondria); Nanoparticles interact with mitochondria by either disrupting the mitochondrial membrane potential, or accumulation in the mitochondria. This is another possible route to production of peroxide species. There is evidence in the literature about the presence of gold (Pan Y 2009; Liming Wang 2011), silver (Martin Kruszewski Chapter 5 Advances in Molecular toxicology Vol.5 2011) and Zinc oxide nanoparticles in mitochondria and production of ROS. Characterizing ROS damage: The damage caused by nanoparticles can be assessed trough following ways: MTT essay to assess the mitochondrial damage caused by the nanoparticles and ROS. Signs of apoptosis and inflammation can be checked using LDH assay. Also using transcriptomic and genomic methods can be adapted to analyze the cellular response to incoming nanoparticles, and post ROS response. Electron Microscopy to visually analyze the damage (swelling of organelles or cell(s)) Conclusion: There is overwhelming evidence that nanoparticles indeed produce (directly or indirectly) reactive oxygen species. These are early days, and we are still in dark waters until we understand and confirm the mechanism of ROS production by nanoparticles.
  • 7. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham References: Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Patrick L Apopa, Yong Qian, Rong Shao, Nancy L Guo, Diane Schwegler-Berry, Maricica Pacurari, Dale Porter, Xianglin Shi, Val Vallyathan, Vincent Castranova and Daniel C Flynn. Particle and Fibre Toxicology 2009, 6:1 Selective Targeting of Gold Nanorods at the Mitochondria of Cancer Cells: Implications for Cancer Therapy Liming Wang, Ying Liu, Wei Li, Xiumei Jiang, Yinglu Ji, Xiaochun Wu, Ligeng Xu, Yang Qiu, Kai Zhao, Taotao Wei Yufeng Li, Yuliang Zhao, and Chunying Chen. pubs.acs.org/NanoLett. Nano Lett. 2011, 11, 772–780 Antifungal activity of ZnO nanoparticles—the role of ROS mediated cell injury. Anat Lipovsky, Yeshayahu Nitzan, Aharon Gedanken and Rachel Lubart. Anat Lipovsky et al 2011 Nanotechnology 22 105101 Gold Nanoparticles of Diameter 1.4nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage. Pan, Y., Leifert, A., Ruau, D., Neuss, S., Bornemann, J., Schmid, G., Brandau, W., Simon, U. and Jahnen-Dechent, W. (2009), Small, 5: 2067–2076. doi: 10.1002/smll.200900466. Mitochondrial formation of reactive oxygen species. The Journal of Physiology, 552: 335–344. doi: 10.1111/j.1469-7793.2003.00335.x. Turrens, J. F. (2003) Reactive oxygen species: Metabolism, Oxidative Stress, and Signal Transduction. Klaus Apel and Heribert Hirt. Annu. Rev. Plant Biol. 2004. 55:373–99 doi: 10.1146/annurev.arplant.55.031903.141701 Cytotoxicity of Nanoparticles. Nastassja Lewinski, Vicki Colvin, and Rebekah Drezek. small 2008, 4, No. 1, 26 – 49. Effects of Surface Chemistry on Cytotoxicity, Genotoxicity, and the Generation of Reactive Oxygen Species Induced by ZnO Nanoparticle. Hong Yin, Philip S. Casey, Maxine J. McCall, and Michael Fenech Langmuir 2010 26 (19), 15399-15408 Copper Oxide Nanoparticles Are Highly Toxic: A Comparison between Metal Oxide Nanoparticles and Carbon Nanotubes Hanna L. Karlsson, Pontus Cronholm, Johanna Gustafsson, and Lennart Moller Chemical Research in Toxicology 2008 21 (9), 1726-1732 The internal structure of mitochondria. Terrence G. Frey and Carmen A. Mannella. TIBS 25th July 2000
  • 8. Name: Adwait Suratkar; UID: 1213672 Department of Earth, Environmental Science and Geography University of Birmingham Unmodified Cadmium Telluride Quantum Dots Induce Reactive Oxygen Species Formation Leading to Multiple Organelle Damage and Cell Death. Jasmina Lovri, Sung Ju Cho,Franc¸oise M. Winnik, and Dusica MaysingerChemistry & Biology, Vol. 12, 1227–1234, November, 2005, Oxidative mechanisms in toxicity of Metal ions. S. J. Stohs and D. Bagchi. Free Radical Biology & Medicine, Vol. 18, No. 2, pp. 321-336, 1995. Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective mélanie auffan, Jérôme rose, Jean-yves bottero, gregory V. lowry, Jean-Pierre Jolivet, and mark r. Wiesner. doi: 10.1038/nnano.2009.242 Nature nanotechnology, Vol. 4 October 2009 Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells Eun- Jung Parka, Jongheop Yib, Kyu-Hyuck Chungc, Doug-Young Ryud, Jinhee Choie, Kwangsik Parka. Toxicology Letters 180 (2008) 222–229 Understanding biophysicochemical interactions at the nano–bio interface Andre e. nel1, lutz mädler, darrell Velego, tian Xia1, eric m. V. hoek, Ponisseril somasundaran, Fred Klaessig, Vince Castranova and mike Thompson. doi: 10.1038/nmat2442, Nature materials Review article Vol 8 july 2009.

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