SLIDE 1
Nanotoxicity Nanotoxicity R We heading towards right R We heading towards right direction direction… …??? ???
SLIDE 2 Presented by Presented by
Introduction and Introduction and nano nano hazards hazards-
Anshika
Reasons for Reasons for nanotoxicity nanotoxicity-
Anant
Screening strategies Screening strategies-
Saranath
ecofriendly ecofriendly approaches approaches-
Upender
Conclusion Conclusion-
Upender
SLIDE 3
What is nanotechnology??? What is nanotechnology???
Nanotechnology is the convergence of Nanotechnology is the convergence of various fields of science, leading to the various fields of science, leading to the development of structures, devices and development of structures, devices and systems that have novel functional systems that have novel functional properties with size ranging between 1 properties with size ranging between 1 and 100 nm. and 100 nm.
SLIDE 4
Nano: The smaller, the better Nano: The smaller, the better
SLIDE 5 Y Nano is so attractive??? Y Nano is so attractive???
small size (surface area and size distribution), small size (surface area and size distribution),
Chemical composition (purity, Chemical composition (purity, crystallinity crystallinity, , electronic properties, etc.), electronic properties, etc.),
surface structure (surface reactivity, surface surface structure (surface reactivity, surface groups, inorganic or organic coatings, etc.), groups, inorganic or organic coatings, etc.),
solubility, solubility,
shape, shape,
aggregation. aggregation.
SLIDE 6 Singh et al 2009
Application on nanomaterials in different sectors
SLIDE 7 NANOTOXICITY NANOTOXICITY
Toxic effect of Toxic effect of nanomaterial nanomaterial on biological
system and environment. system and environment.
Nanotoxicology Nanotoxicology
is a branch
is a branch
bionanoscience bionanoscience which deals with the study which deals with the study and application
toxicity
and application
toxicity
nanomaterials nanomaterials. .
SLIDE 8
Types of exposure to Types of exposure to nanmaterials nanmaterials
Short term concern Short term concern
Occupational Occupational
Consumer Consumer Long term concern Long term concern
enviromental enviromental
SLIDE 9 Routes of exposure, uptake, Routes of exposure, uptake, distribution and degradation of NP distribution and degradation of NP
,
Oberdörster et al 2005
SLIDE 10 Possible nanoparticle modifications in the environment.
Oberdörster et al 2005
SLIDE 11 Entry of nanomaterial inside body (intra venous, dermal, subcutaneous, inhalation, intraperitoneal, and oral) interaction at biological surface (Absorption) Remain unchanged/ Modified/ metabolized
Accumulates
Excretes
Fate of nanomaterial in biological systems
SLIDE 12 Possible ways of entry of Possible ways of entry of nanomaterial nanomaterial in cell in cell
Singh et al 2009
SLIDE 13
Toxic effects on health Toxic effects on health… …
Allergy Allergy
Deposition in different organs : can lead Deposition in different organs : can lead to organ failure to organ failure
Inflammation. Inflammation.
Cytotoxicity Cytotoxicity
Tissue damage Tissue damage
ROS generation ROS generation
DNA damage DNA damage
SLIDE 15 Oberdörster et al 2005
SLIDE 16 Oberdörster G. et al 2005
SLIDE 17 DNA DNA-
Fullerene interaction
SLIDE 18 Hypothetical cellular interaction of NSPs (adapted from Donaldson and Tran 2002). EGFR, epidermal growth factor receptor. Inflammation and oxidative stress can be mediated by several primary pathways: a) the particle surface causes oxidative stress resulting in increased intracellular calcium and gene activation; b) transition metals released from particles result in oxidative stress, increased intracellular calcium, and gene activation; c) cell surface receptors are activated by transition metals released from particles, resulting in subsequent gene activation; or d) intracellular distribution of NSPs to mitochondria generates oxidative stress.
Oberdörster G. et al 2005
SLIDE 19
Reasons for Toxicity Reasons for Toxicity
High surface area to volume ratio. High surface area to volume ratio.
Surface active groups/Chemical Surface active groups/Chemical composition composition
Shape Shape complementarity complementarity to to biomolecules biomolecules
Accumulation in the system Accumulation in the system
SLIDE 20 Karakoti et al 2006
SLIDE 21 Oberdörster G. et al 2005
SLIDE 22
Inhibition of enzymes. Inhibition of enzymes.
SLIDE 23 Screening strategies Screening strategies
Nanomaterials Nanomaterials Toxic Toxic Non Non-
toxic
SLIDE 24 Assessment paradigm Assessment paradigm
In In-
- depth characterization of
depth characterization of nanomaterials nanomaterials ( (NMs NMs) before ) before cytotoxicity cytotoxicity studies studies
Assessment of toxicity based on cell cycle Assessment of toxicity based on cell cycle pathways pathways – – Cytotoxicity Cytotoxicity assays assays
Oberdorster et al 2005
SLIDE 25 In vitro In vitro CYTOTOXICITY ASSAYS CYTOTOXICITY ASSAYS
Cell viability Cell viability
– – Detection of mitochondrial activity Detection of mitochondrial activity – – Lactate Lactate Dehydrogenase Dehydrogenase assay assay – – Propidium Propidium iodide iodide staining staining – – Neutral Red Neutral Red staining staining – – Detection of Detection of Caspase Caspase-
3
Cellular stress response Cellular stress response
Inflammatory response Inflammatory response
Kroll Kroll et al et al 2006 2006
SLIDE 26 DNA damaging Potential of DNA damaging Potential of ZnO ZnO Nanoarticles Nanoarticles
Widely used as ingredient of cosmetics Widely used as ingredient of cosmetics
Due to extremely small size, they are Due to extremely small size, they are taken up by epidermal taken up by epidermal (skin) cells (skin) cells
Even at low concentrations, they possess Even at low concentrations, they possess genotoxic genotoxic (DNA (DNA – – damaging) potential damaging) potential
It is mediated through lipid It is mediated through lipid peroxidation peroxidation and oxidative stress and oxidative stress
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 27 ZnO ZnO nanoparticles induced nanoparticles induced cytotoxicity cytotoxicity
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 28 MTT ASSAY MTT ASSAY
MTT Assay of human epidermal cells exposed to 30nm ZnO nanoparticles
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 29 LDH ASSAY LDH ASSAY
LDH Assay of human epidermal cells exposed to 30nm ZnO nanoparticles
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 30 Neutral Red Uptake Neutral Red Uptake
NR Assay of human epidermal cells exposed to 30nm ZnO nanoparticles
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 31 Death of cells due to Death of cells due to genotoxicity genotoxicity
- V. Sharma et al / Toxicology Letters 185 (2009) 211–218
SLIDE 32 Predictive assessment methods Predictive assessment methods
Reliable and reproducible screening Reliable and reproducible screening protocols are needed protocols are needed
It is challenging because of the large It is challenging because of the large number of new number of new nanomaterials nanomaterials that are that are produced continually, their host of novel produced continually, their host of novel physico physico-
chemical properties, and uncertainty in how those properties may uncertainty in how those properties may relate to biological outcomes relate to biological outcomes
Meng et al 2009
SLIDE 33 Contd. Contd.
Predict the hazard potential of a series of Predict the hazard potential of a series of ambient particles that differ in composition ambient particles that differ in composition based on impact on cellular pathway based on impact on cellular pathway
Example is hierarchical oxidative stress Example is hierarchical oxidative stress paradigm which classifies responses as paradigm which classifies responses as anti anti-
- oxidant defense, inflammation and
- xidant defense, inflammation and
cytotoxicity cytotoxicity
Meng et al 2009
SLIDE 34 Contd. Contd.
Use of hierarchical oxidative stress assessment to make predictions about nanomaterial hazards
Meng et al 2009
SLIDE 35 High High – – throughput screening throughput screening
Screening of multiple Screening of multiple nanomaterials nanomaterials at at multiple concentrations with multiple cell multiple concentrations with multiple cell lines, simultaneously. lines, simultaneously.
Enabled through the miniaturization and Enabled through the miniaturization and multiplexing of the experimental multiplexing of the experimental apparatus apparatus
Integration and automation of quantitative Integration and automation of quantitative fluorescence microscopy and image fluorescence microscopy and image analysis analysis
Jan et al 2008
SLIDE 37 Zebrafish Zebrafish as screening tool as screening tool
Small size of Small size of zebra zebrafi
fish
sh embryos allows facile, embryos allows facile, economic medium through economic medium through-
put screening
Nanotoxicity is quantified based on phenotypic Nanotoxicity is quantified based on phenotypic changes of the changes of the zebra zebrafi
fish
sh embryos, ranging from embryos, ranging from 0 ( 0 (normalphenotype normalphenotype) ) 1 (minor phenotypic changes) 1 (minor phenotypic changes) 2 (moderate alterations) 2 (moderate alterations) 3 (severe embryo deformation) 3 (severe embryo deformation) 4 (embryo death). 4 (embryo death).
Fako and Furgeson, 2009
SLIDE 38 Fako and Furgeson, 2009
SLIDE 39 LIMITATIONS OF CURRENT in LIMITATIONS OF CURRENT in-
vitro CYTOTOXICITY STUDIES CYTOTOXICITY STUDIES
Most in Most in-
vitro cytotoxicity cytotoxicity experiments experiments carried out so far have used particles not carried out so far have used particles not well characterized regarding composition well characterized regarding composition
physico-
chemical properties
Characterization is mandatory since Characterization is mandatory since nanoparticles might interact with assay nanoparticles might interact with assay components or interfere with detection components or interfere with detection systems resulting in unreliable data systems resulting in unreliable data
Kroll Kroll et al et al 2006 2006
SLIDE 40
Use test systems that cannot be Use test systems that cannot be influenced by influenced by nanospecific nanospecific properties such properties such as as
– – High adsorption capacity High adsorption capacity – – Optical Properties Optical Properties – – Catalytic Activity Catalytic Activity – – Acidity/Alkalinity Acidity/Alkalinity – – Magnetic Properties Magnetic Properties – – Dissolution Dissolution
Kroll Kroll et al et al 2006 2006
SLIDE 41
Can Can nanomaterial nanomaterial be made be made ecofriendly ecofriendly?? ??
Manipulating nanomaterials structure to suppress the toxic properties.
Surface modifications
Tailored coatings,
On-board packaging,
special disposal strategies.
SLIDE 42 Research priorities for eco-responsible design and disposal of manufactured nanomaterials.
Alvarez Alvarez et al et al 2009 2009
SLIDE 43 Conclusion….
Oberdörster et al 2005
