Nanotoxicity Nanotoxicity R We heading towards right R We heading towards right direction… …??? ??? direction
Presented by Presented by Introduction and nano nano hazards hazards- - Anshika Anshika Introduction and Reasons for nanotoxicity nanotoxicity- - Anant Anant Reasons for Screening strategies- - Saranath Saranath Screening strategies ecofriendly approaches approaches- - Upender Upender ecofriendly Conclusion- - Upender Upender Conclusion
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.
Nano: The smaller, the better Nano: The smaller, the better
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, crystallinity crystallinity, , Chemical composition (purity, 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.
Application on nanomaterials in different sectors Singh et al 2009
NANOTOXICITY NANOTOXICITY Toxic effect of nanomaterial nanomaterial on biological on biological Toxic effect of system and environment. system and environment. Nanotoxicology Nanotoxicology is a branch of is a branch of bionanoscience which deals with the study which deals with the study bionanoscience and application of toxicity of and application of toxicity of nanomaterials. . nanomaterials
Types of exposure to nanmaterials nanmaterials Types of exposure to Short term concern Short term concern Occupational Occupational Consumer Consumer Long term concern Long term concern enviromental enviromental
Routes of exposure, uptake, Routes of exposure, uptake, distribution and degradation of NP distribution and degradation of NP , Oberdörster et al 2005
Possible nanoparticle modifications in the environment. Oberdörster et al 2005
Fate of nanomaterial in biological systems Entry of nanomaterial inside body (intra venous, dermal, subcutaneous, inhalation, intraperitoneal, and oral ) interaction at biological surface (Absorption) Remain unchanged/ Accumulates Modified/ Excretes metabolized
Possible ways of entry of Possible ways of entry of nanomaterial in cell in cell nanomaterial Singh et al 2009
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
Neil et al 2006
Oberdörster et al 2005
Oberdörster G. et al 2005
DNA- -Fullerene interaction Fullerene interaction DNA
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
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 complementarity complementarity to to biomolecules biomolecules Shape Accumulation in the system Accumulation in the system
Karakoti et al 2006
Oberdörster G. et al 2005
Inhibition of enzymes. Inhibition of enzymes.
Screening strategies Screening strategies Nanomaterials Nanomaterials Toxic Non- -toxic toxic Toxic Non
Assessment paradigm Assessment paradigm In- -depth characterization of depth characterization of nanomaterials nanomaterials In (NMs NMs) before ) before cytotoxicity cytotoxicity studies studies ( Assessment of toxicity based on cell cycle Assessment of toxicity based on cell cycle pathways – – Cytotoxicity Cytotoxicity assays assays pathways Oberdorster et al 2005
In vitro CYTOTOXICITY ASSAYS CYTOTOXICITY ASSAYS In vitro 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 3 – Cellular stress response Cellular stress response Inflammatory response Inflammatory response Kroll et al et al 2006 2006 Kroll
DNA damaging Potential of ZnO ZnO DNA damaging Potential of 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 (skin) cells (skin) cells taken up by epidermal Even at low concentrations, they possess Even at low concentrations, they possess genotoxic (DNA (DNA – – damaging) potential damaging) potential genotoxic It is mediated through lipid peroxidation peroxidation It is mediated through lipid and oxidative stress and oxidative stress V. Sharma et al / Toxicology Letters 185 (2009) 211–218
ZnO nanoparticles induced nanoparticles induced cytotoxicity cytotoxicity ZnO V. Sharma et al / Toxicology Letters 185 (2009) 211–218
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
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
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
Death of cells due to Death of cells due to genotoxicity genotoxicity V. Sharma et al / Toxicology Letters 185 (2009) 211–218
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 nanomaterials nanomaterials that are that are number of new produced continually, their host of novel produced continually, their host of novel physico- -chemical properties, and chemical properties, and physico uncertainty in how those properties may uncertainty in how those properties may relate to biological outcomes relate to biological outcomes Meng et al 2009
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- -oxidant defense, inflammation and oxidant defense, inflammation and anti cytotoxicity cytotoxicity Meng et al 2009
Contd. Contd. Use of hierarchical oxidative stress assessment to make predictions about nanomaterial hazards Meng et al 2009
High – – throughput screening throughput screening High Screening of multiple nanomaterials nanomaterials at at Screening of multiple 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
Jan et al 2008
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