nanotoxicology and nanosafety

NANOPARTICLES AND NANOSAFETY

REPORTER: Mike K . K .AGBOOLA ADVISOR: Tet iana NEBESNA

National O.O. Bogomolets Medical UniversityDepartment of pharmacology and clinical

pharmacology Chief of department: prof. I.S. Chekman

INTRODUCTION

small is beautiful.......... DANGERS COME IN SMALL PARTICLES

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

G R A P H E N E

C A R B O N N A N O T U B E

C 6 0 B U C K M I N S T E R F U L L E R E N E

BIOLOGISTS COUNTER THAT NANOCARBON IS A RECENT DISCOVERYTHEY’VE BEEN STUDYING DNA AND RNA

FOR MUCH LONGER(AND ARE ALREADY USING IT TO

TRANSFORM OUR WORLD)

All of these things ARE very small

INDEED, THEY ARE ALL ABOUT THE SIZE OF A NANOMETER:

NANO = 10 - 9 = 1/ 1,000,000,000 = 1 / BILLIONA NANOMETER IS ABOUT THE SIZE OF TEN

ATOMS IN A ROW

THIS LEADS TO ONE COMMONLY USED DEFINITION OF NANOSCIENCE:

NANOSCIENCE IS THE STUDY OF NANOMETER SIZE THINGS (?)

WHY THE QUESTION MARK? BECAUSE WHAT IS SO SPECIAL ABOUT A NANOMETER?

A MICROMETER IS ALSO AWFULLY SMALL:MICRO = 10 - 6 - 1 /1,000,000 = 1 / MILLIONA MICROMETER (OR "MICRON") IS ~ THE

SIZE OF LIGHT'S WAVELENGTH

Size of Things (violet = man-made things)

M I L L I M E T E R S M I C R O N S N A N O M E T E R S

B A L L O F A B A L L P O I N T P E N 0 . 5T H I C K N E SS O F PA P E R 0 . 1 1 0 0

H U M A N H A I R 0 . 0 2 - 0 . 2 2 0 – 2 0 0TA L C U M P O W D E R 4 0F I B E R G L A SS F I B E R S 1 0C A R B O N F I B E R 5

H U M A N R E D B LO O D C E L L 4 – 6E - C O L I B A C T E R I U M 1

S I Z E O F A M O D E R N T R A N S I S T O R 0 . 2 52 5 0

S I Z E O F S M A L L P OX V I R U S 0 . 2 – 0 . 32 0 0 – 3 0 0

E L E C T R O N WAV E L E N GT H : ~ 1 0 N M O R L E SS D I A M E T E R O F C A R B O N N A N O T U B E

3D I A M E T E R O F D N A S P I R A L

2D I A M E T E R O F C 6 0 B U C K Y B A L L

0 . 7D I A M E T E R O F B E N Z E N E R I N G

0 . 2 8

S I Z E O F O N E AT O M ~ 0 . 1

NANOSCIENCE IS FUNDED BY EUROPEAN UNION GOVERNMENT:

TOTAL BUDGET FOR 2007 – 2013 YEARS IS € 3.5 BILLION

Now emphasis is given to the following activities: Nanosciences and nanotechnologies - studying phenomena and

manipulation of matter at the nanoscale and developing nanotechnologies leading to the manufacturing of new products and services.

Materials - using the knowledge of nanotechnologies and biotechnologies for new products and processes.

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.

Integration of technologies for industrial applications - focusing on new technologies, materials and applications to address the needs identified by the different European Technology Platforms.

NANOPARTICLES

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.

TYPES AND PROPERTIES OF NPS:

NATURALINCIDENTAL ENGINEERED NANOPARTICLES

Both natural and incidental nanoparticles may have irregular or regular shapes, while engineered NPs most often have regular shapes, such tubes, sphere, rings.

CLASSIFICATION OF Engineered nanoparticles

carbon-based materials (nanotubes, fullerenes),

metal-based materials (including both metal oxides and quantum dots),

dendrimers (nano-sized polymers built from branched units of unspecified chemistry), and

composites (including nanoclays).

Survey of NPs, in vivo characterization and biological areas of concern

Nanostructur, Application (example), Concerns, Mechanistic areas of interest

Metal nanoparticles: Contrast agents; drug delivery: Element specific toxicity Excretion reactive oxygen species  Nanoshells Hyperthermia therapy Genotoxicity Excretion Fullerenes Vaccine adjuncts; Hyperthermia therapy Antibody generation Immunotoxicity Quantum dots Fluorescent contrast agent Metabolism ,Cytotoxicity

Intracellular/ organ edistribution; redistribution; excretion

Polymer Nanoparticles Drug delivery; therapeutics Unknown Metabolism;

immunotoxicity; complement

activation Dendrimer Guest delivery of drug/ Radiolabel dose Metabolic path Surface chemistry

and

elementaleffects; complement a activation

Liposome Drug delivery; contrast Agent vehicle Hypersensitivity reactions Complement

activation models for artificial cells

Purpose of work

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

Characterization

Scheme of problems

toxicity itself can be useful as it is highly sought for in certain applications-cancer therapies

consumer resistance that arose at the introduction of products using genetically modified organisms (GMOs)

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

Analytical Aspect

Test engineering and measuring Particles concentrationSize and form, agglomerateParticle Surface charge, coating after synthesis, within

the environmentDissolution and recombination

WAYS OF ASSIMILATION AND INCORPORATION

Modes of action and mechanismsLymphatic systemBlood systemNervous systemsCells-cell interactionUptake in the cells and the nucleus

Kinds of toxicity

Bio-degradation Bio-accumulationAnimal toxicity GenotoxicityEcotoxicity Cytotoxicity

Mechanism of NPs toxicity development

Reactive Oxygen Species(ROS)free radical releaseoxidative stress inflammation and consequent damage to proteins, membranes

and DNA

Nanomedicine Application Area: Therapy Techniques

Molecular diagnostics, nanodiagnostics, and improvements in the discovery, design and delivery of drugs, including nanopharmaceuticals

Surgery-Nanorobots Cancer (nanooncology), Neurological disorders (nanoneurology), Cardiovascular disorders (nanocardiology), Diseases of bones and joints

(nanoorthopedics), Diseases of the eye (nanoophthalmology), and Infectious diseases.

Nanosafety:Tumor-Seeking Nanoparticles

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

REGULATIONS

RISK = HAZARD + EXPOSURE (ASSESSMENT)

the implications for toxicology and the risk of human health and environment

·         Hazard·         Risk·         Exposure nature, concentration and period ·         Dose

NANOSAFETY:SAFETY STANDARD

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

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

USING NANOPARTICLES: NANO-X-RAY

Enhaced tumor cell death No toxicityMajor advantage over standard radiotherapy

treatment (No exposure to free radicals as in radiotherapy)

Amplifying X-ray effectsInjection directly into the tumors without

unnecessary interaction Allowing targeted cells of the tumorsCombats range of cancer variety

Decreasing Toxicity

Insoluble or nearly insoluble ultrafine particlesDemonstration on 3D before clinical trialsDevelop models,in vitro and in vivo for

interaction with the human body to assessing TOXICITY, BIODISTRIBUTION, ALLERGIES

The potential risk of using untested nanomaterials in personal care products SHOULD BE DISCOURAGED

The use of nanoparticles in cosmetics and sunscreen should be put to check by standard GRAS(Generally Recognised As Safe) for NPs.

Benefits and Goodnews

Nanosizing can also lead to a more economical utilization of expensive materials-meaning that can use less material because the reactions are more efficient.

Not all NPs are dangerous

Conclusion

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.

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.

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.

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THANK YOU FOR ATTENTION!

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