Nanotoxicology and Nanosafety


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  • Active tumor targeting of nanoparticles involves attaching molecules, known collectively as ligands, to the outsides of nanoparticles. These ligands are special in that they can recognize and bind to complementary molecules, or receptors, found on the surface of tumor cells. When such targeting molecules are added to a drug delivery nanoparticle, more of the anticancer drug finds and enters the tumor cell, increasing the efficacy of the treatment and reducing toxic effects on surrounding normal tissue.
  • Nanotoxicology and Nanosafety

    1. 1. National O.O. Bogomolets Medical UniversityDepartment of pharmacology and clinical pharmacologyChief of department: prof. I.S. Chekman<br />NANOPARTICLES AND NANOSAFETY<br />REPORTER: Mike K. K.AGBOOLA<br /> ADVISOR: Tetiana NEBESNA<br />
    2. 2. INTRODUCTION<br /> small is beautiful.......... DANGERS COME IN SMALL PARTICLES <br />
    3. 3. What IS Nanoscience?When people talk about Nanoscience, they start by describing thingsPhysicists and Material Scientists point to things like new nanocarbon materials: They effuse (radiate)about nanocarbon’s strength and electrical properties<br />Graphene<br />Carbon Nanotube<br />C60 Buckminster Fullerene<br />
    4. 4. Biologists counter that nanocarbon is a recent discovery<br />THEY’VE been studying DNA and RNA for much longer<br /> (And are already using it to transform our world)<br />
    5. 5. All of these things ARE very small<br />Indeed, they are all about the size of a nanometer:<br />Nano = 10-9 = 1/ 1,000,000,000 = 1 / Billion<br />A nanometer is about the size of ten atoms in a row<br />This leads to ONE commonly used definition of nanoscience:<br />Nanoscience is the study of nanometer size things (?)<br />Why the question mark? Because what is so special about a nanometer?<br /> A micrometer is ALSO awfully small:<br /> Micro = 10-6 - 1/1,000,000 = 1 / Million<br /> A micrometer (or "micron") is ~ the size of light's wavelength<br />
    6. 6. Size of Things (violet = man-made things)<br />Millimeters Microns Nanometers<br />Ball of a ball point pen 0.5<br />Thickness of paper 0.1 100<br />Human hair 0.02 - 0.2 20 – 200<br />Talcum Powder 40<br />Fiberglass fibers 10<br />Carbon fiber 5<br />Human red blood cell 4 – 6<br />E-coli bacterium 1<br />Size of a modern transistor 0.25 250<br />Size of Smallpox virus 0.2 – 0.3 200 – 300<br /> Electron wavelength: ~10 nm or less <br />Diameter of Carbon Nanotube 3<br />Diameter of DNA spiral 2<br />Diameter of C60 Buckyball 0.7<br />Diameter of Benzene ring 0.28<br />Size of one Atom~0.1<br />
    7. 7. NANOSCIENCE IS FUNDED BY EUROPEAN UNION GOVERNMENT: TOTAL BUDGET FOR 2007 – 2013 YEARS IS € 3.5 BILLION<br />Now emphasis is given to the following activities:<br />Nanosciences and nanotechnologies - studying phenomena and manipulation of matter at the nanoscale and developing nanotechnologies leading to the manufacturing of new products and services. <br />Materials - using the knowledge of nanotechnologies and biotechnologies for new products and processes. <br />New production - creating conditions for continuous innovation and for developing generic(suitable for broad range) production 'assets' (technologies, organisation and production facilities as well as human resources), while meeting safety and environmental requirements. <br />Integration of technologies for industrial applications - focusing on new technologies, materials and applications to address the needs identified by the different European Technology Platforms. <br />
    8. 8. NANOPARTICLES<br />Nanoparticles materials (nanomaterials, nanoscale), are a broadly defined set of substances that have at least one critical dimension less than 100nm (0.1micron) and possess unique optical, magnetic, or electrical properties. <br />
    9. 9. TYPES AND PROPERTIES OF NPS:<br />NATURAL<br />INCIDENTAL <br />ENGINEERED NANOPARTICLES <br />Both natural and incidental nanoparticles may have irregular or regular shapes, while engineered NPs most often have regular shapes, such tubes, sphere, rings.<br />
    10. 10. CLASSIFICATION OF Engineered nanoparticles<br />carbon-based materials (nanotubes, fullerenes), <br />metal-based materials (including both metal oxides and quantum dots), <br />dendrimers (nano-sized polymers built from branched units of unspecified chemistry), and <br />composites (including nanoclays).<br />
    11. 11.
    12. 12. Survey of NPs, in vivo characterization and biological areas of concern<br />Nanostructur, Application (example), Concerns, Mechanistic areas of interest <br />Metal nanoparticles: Contrast agents; drug delivery: Element specific toxicity Excretion<br /> reactive oxygen species<br /> <br />Nanoshells Hyperthermia therapy Genotoxicity Excretion <br />Fullerenes Vaccine adjuncts; <br /> Hyperthermia therapy Antibody generation Immunotoxicity <br />Quantum dots Fluorescent contrast agent Metabolism ,Cytotoxicity Intracellular/ organ edistribution; redistribution; excretion<br />Polymer<br />Nanoparticles Drug delivery; therapeutics Unknown Metabolism; immunotoxicity;<br /> complement activation<br />Dendrimer Guest delivery of drug/<br /> Radiolabel dose Metabolic path Surface chemistry and <br /> elementaleffects; complement a activation<br />Liposome Drug delivery; contrast <br /> Agent vehicle Hypersensitivity reactions Complement activation <br /> models for artificial cells<br />
    13. 13. Purpose of work<br />evaluation and understanding of the dependence of toxic and safety effects on the shape, size, initial material, surface area, electric charge, and other physicochemical structural peculiarities, as well as on the dosage, mode of application, concentration in the target organ, and duration of action<br />
    14. 14. Characterization<br />
    15. 15. Scheme of problems<br />toxicity itself can be useful as it is highly sought for in certain applications-cancer therapies<br />consumer resistance that arose at the introduction of products using genetically modified organisms (GMOs)<br /> if toxicity is known, Questions that have also been raised about the safety of engineered nanomaterials in consumer products or in implantable medical devices could be alleviated by devising a special or targeted delivery system<br />
    16. 16. Analytical Aspect<br /><ul><li>Test engineering and measuring
    17. 17. Particles concentration
    18. 18. Size and form, agglomerate
    19. 19. Particle Surface </li></ul> charge, coating after synthesis, within the environment<br /><ul><li>Dissolution and recombination</li></li></ul><li>WAYS OF ASSIMILATION AND INCORPORATION<br />Modes of action and mechanisms<br />Lymphatic system<br />Blood system<br />Nervous systems<br />Cells-cell interaction<br />Uptake in the cells and the nucleus<br />
    20. 20. Kinds of toxicity<br />Bio-degradation <br />Bio-accumulation<br />Animal toxicity <br />Genotoxicity<br />Ecotoxicity <br />Cytotoxicity<br />
    21. 21. Mechanism of NPs toxicity development<br />Reactive Oxygen Species(ROS)<br />free radical release<br />oxidative stress<br /> inflammation and <br />consequent damage to proteins, membranes and DNA<br />
    22. 22. Nanomedicine Application Area: Therapy Techniques<br /><ul><li> Molecular diagnostics, nanodiagnostics, and improvements in the discovery, design and delivery of drugs, including nanopharmaceuticals
    23. 23. Surgery-Nanorobots
    24. 24. Cancer (nanooncology),
    25. 25. Neurological disorders (nanoneurology),
    26. 26. Cardiovascular disorders (nanocardiology),
    27. 27. Diseases of bones and joints (nanoorthopedics),
    28. 28. Diseases of the eye (nanoophthalmology), and
    29. 29. Infectious diseases. </li></li></ul><li>Nanosafety:Tumor-Seeking Nanoparticles<br />In this image, targeted nanoparticles - each about 1/100th the size of a human cell and engineered to be stealthy within the body--deliver high doses of chemotherapy to cancer cells<br />
    30. 30. REGULATIONS<br />
    31. 31. RISK = HAZARD + EXPOSURE (ASSESSMENT)<br /> the implications for toxicology and the risk of human health and environment<br />·         Hazard<br />·         Risk<br />·         Exposure<br /> nature, concentration and period <br />·         Dose<br />
    32. 32. NANOSAFETY:SAFETY STANDARD<br />nanotechnology has removed much of the “magic” to yield 21st century “smart bombs” capable of carrying a whole host of new anticancer drugs directly to tumors<br />ecological risk assessment is essential to understand environmental implications of nanomaterials. The fate of nanomaterials in aqueous environment is controlled by many biotic/abiotic processes such as solubility /dispersability, size, shape, form interactions between the nanomaterials and natural/anthropogenic chemicals in the ecosystem<br />
    33. 33. USING NANOPARTICLES: NANO-X-RAY<br />Enhaced tumor cell death <br />No toxicity<br />Major advantage over standard radiotherapy treatment (No exposure to free radicals as in radiotherapy)<br />Amplifying X-ray effects<br />Injection directly into the tumors without unnecessary interaction <br />Allowing targeted cells of the tumors<br />Combats range of cancer variety<br />
    34. 34. Decreasing Toxicity<br />Insoluble or nearly insoluble ultrafine particles<br />Demonstration on 3D before clinical trials<br />Develop models,in vitro and in vivo for interaction with the human body to assessing TOXICITY, BIODISTRIBUTION, ALLERGIES<br />The potential risk of using untested nanomaterials in personal care products SHOULD BE DISCOURAGED<br />The use of nanoparticles in cosmetics and sunscreen should be put to check by standard GRAS(Generally Recognised As Safe) for NPs. <br />
    35. 35. Benefits and Goodnews<br />Nanosizing can also lead to a more economical utilization of expensive materials-meaning that can use less material because the reactions are more efficient.<br />Not all NPs are dangerous<br />
    36. 36. Conclusion<br />The toxicology and biodynamics of certain (silica) NPs investigated in a mice model revealed that NPs were not toxic and can be used in vivo. This study should not be misunderstood to promote the manufacture of these nanomaterials without detailed assessment of environmental and human risks. <br />Besides the workers in the manufacturing wing, others who get exposed (e.g. occupational health nurses) to NPs should be aware of the potential risks and possible means to avoid health risks. <br />There is a need to identify specific regulatory regimes to protect personnel involved in the production and use of NPs for cosmetic, medical and agricultural purposes.<br />
    37. 37. СПАСИБO<br />THANK YOU FOR ATTENTION!<br />29<br />