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» Nanomaterial Toxicology
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Overview
Technological innovations have led to the emergence of nanotechnology as a new field that will revolutionize industrial development. In fact, manufacture of nanomaterials of various shapes and compositions has increased in the last few years, with a vast potential of use ranging from diagnostic imaging to molecular construction. More than 1000 nanotech based consumer products are already in the market worldwide. Nanodevices are also being used as sensors in diagnosis of human disease. Nanotechnology is associated with unprecedented dimensions related to nanomaterial safety that may affect the consumers, occupational workers and the environment as a whole.
At present, more than 20 countries worldwide are manufacturing and marketing different varieties of nanotech-based consumer products of which cosmetics form the largest category. Due to the large scale use of nanomaterials globally, the dimension of exposure to flora and fauna will be unrestricted as the nanomaterials have the ability to cross the cellular barriers. The biological interaction of the nanomaterials when compared to their bulk counter parts is largely different. This is due to the extremely small size of the nanoparticles (NPs) that may interact directly with macromolecules such as DNA. To assess the safety/toxicity of nanomaterials, it is imperative that proper characterisation is done especially before in vitro/in vivo studies are undertaken.
With the realisation of entirely new dimensions of safety of nanomaterials IITR initiated work in the area of safety/toxicity evaluation of nanomaterials. IITR?s contribution in the field is evident by the publications in peer reviewed journals.The team of scientists working at IITR has the experience both in synthesis as well as safety / toxicity evaluation and impact assessment of engineered nanomaterials (ENMs). Some of the most critical issues that need to be addressed for safety/toxicity assessment of ENMs include: 1) effect of shape & size; 2) dosimetry; 3) route of delivery and tracking; 4) development and validation of test models; 5) in vitro vs. in vivo extrapolation; 6) ecotoxicity; 7) environmental monitoring and 8) life cycle analysis. Therefore, the aim of the group working at IITR is to devise new methods and validate existing techniques that can be applied for safety/toxicity assessment of ENMs and nanodevices.
Mission and goals: To investigate health and environmental effects of nanomaterials to delineate their toxicity and assure safe usage in consumer products and therapeutics.
Competencies: Synthesis and detailed characterization of nanoparticles. Infra-structure facilities and expertise to investigate interactions of different types of nanomaterials with biological systems (from whole organism to molecular level) to evaluate their toxicity. Battery of in vitro and in vivo toxicity assays addressing issues of cytotoxicity, genotoxicity, immunotoxicity, dermal toxicity, neurotoxicity, reproductive toxicity, biodistribution, metabolism, elimination and ecotoxicological impact.

Highlights of work done at IITR:
  1. Zinc and titanium oxide nanoparticles cause DNA damage and oxidative stress
    Our data demonstrates that ZnO NPs even at low concentrations possess a genotoxic potential in human epidermal cells which may be mediated through lipid peroxidation and oxidative stress. A similar response was also observed with TiO2 NPs [Toxicology Letters, 185(3):211-218; 2009].
    The article featured in the European Commission document "Science for Environment Policy - Nanomaterials, Issue 12, page 4, April2009" http://ec.europa.eu/environment/integration/research/newsalert/pdf/12si.pdf
  1. Fullerenes are genotoxic at low concentrations
  2. New Fullerene derivatives obtained by chemical modification are being made and the chemistry of the new C60 and C60 derivatives are being explored in many different fields including organic photovoltaics. At IITR, the study with stable aqueous suspensions of colloidal C60 fullerenes free of toxic organic solvents (ethanol nC60 and aqueous nC60 suspensions) in human lymphocytes revealed a genotoxic potential even at low concentrations [Environmental Science and Technology, 40(23):7394-7401; 2006].
    One of top 20 most accessed article of the journal from Oct - Dec 2006.

  1. Silver nanoparticles cause more DNA damage than gold nanoparticles
    A systematic cytotoxic and genotoxic evaluation of glycolipid-conjugated silver and gold nanoparticles is carried out. These glycolipid nanoparticle conjugates are obtained by exploiting the reductive capability of a class of glycolipids called sophorolipids that play the role of capping agent as well. Further, when tested for their cytotoxicity and genotoxicity on HepG2 cells, these nanoparticles are found to be cytocompatible up to 100 µM metal concentrations. Of the two metallic systems investigated, gold nanoparticles are found to be more cytocompatible than the same concentrations of silver nanoparticles. Similarly, it is also demonstrated that at 100 µM, silver nanoparticles cause more DNA damage compared to gold nanoparticles of similar concentrations [New Journal of Chemistry, 34: 294-301, 2010].
    One of the top ten most accessed article of the journal for February 2010.
  1. Novel nanoconstructs as carriers for nanomedicine for efficient management of solid tumor
    Tumor-specific gene delivery constitutes a primary challenge in nonviral mediated gene therapy. Our studies demonstrated that nanoconstructs of branched polyethylenimine (bPEI, 25 kDa) with a natural polysaccharide, chondroitin sulfate (CS), impart site-specific properties. A library of CS_PEI (CP) nanoconstructs was fabricated by altering the content of CS and evaluated in terms of size, surface charge, morphology, pDNA loading efficiency, pDNA release assay, pDNA protection study, cytotoxicity, and transfection efficiency. The outcome revealed higher concentration of CP-3 nanoconstruct in tumor mass. These findings demonstrate that CP nanoconstructs could be exploited as carriers for nanomedicine for efficient management of solid tumor [ACS Nano: 3 (6); 1493-1505; 2009].
    Reviewed by Nature India (doi:10.1038/nindia.2009.253; Published online 23 July 2009).
  1. Gold nanoparticle probes for detection of enterohemorrhagic Escherichia coli
    Enterohemorrhagic Escherichia coli (E. coli; EHEC) serotype O157:H7 is one of the major pathogens, responsible for the severe disease outbreaks. The optical properties of gold nanoparticles (GNPs) were exploited for detection of stx2 gene representing EHEC signature of E. coli O157:H7. The spectral shift in the plasmon band due to aggregation of GNP probes demonstrated the feasibility of a simple and quick colorimetric "spot and read? test in contrast to amplification based detection methods [Journal of Nanoscience and Nanotechnology: 10; 1-5, 2010].
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