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Keywords
NANOPARTICLES, CARBON NANOTUBES, REDOX MODULATION, MODULATION OF INFLAMMATORY RESPONSE, TRANSEPITHELIAL PERMEABILITY, GENOTOXICITY, METAL NANOPARTICLES, STEM CELLS, AUTONOMIC NERVOUS SYSTEM

Interaction of novel nanoparticulate materials with biological systems: testing models for human health risk assessment

Università degli Studi di Parma
Abstract
Nanostructured materials (NM) play a key role in nanotechnology based innovations and their production rates are expected to increase exponentially in the next few years. NM exhibit entirely new physicochemical properties as compared to bulk materials. Carbon nanotubes (CNT), nanowires, quantum dots and metal oxides have received enormous attention since their use may lead to the creation of new analytical tools for biotechnology and life sciences. However, the size of nanoparticles (NP, particles smaller than 100 nanometers in at least one dimension) and their surface characteristics may profoundly affect cell behaviour. Thus, concerns have been raised about NP adverse effects on biological systems and, possibly, consequent health risks. There is evidence that NP entry the body through a number of routes, including inhalation and skin permeation. Once in the body, NP seem to penetrate into the cells more rapidly than larger particles and, therefore, to move more easily to distant sites within the body. This fact may explain why NP, e.g of metallic elements or CNT, exert greater cytotoxic and genotoxic effects than larger particles of the same substance at the same mass concentration. Although the mechanism of this toxicity is not fully established, an accepted hypothesis is that NP induce reactive oxygen and nitrogen species production, thus leading to oxidative stress both in lipis and nucleic acids and influencing calcium and sulphydryl homeostasis.
Relying on the >>>

Principal Investigator
Enrico Bergamaschi Università degli Studi di PARMA
Research Objectives
Relying on the collaboration of researchers with different scientific backgrounds (Occupational Medicine, Industrial Toxicology, Biology, General Pathology, Genetics, Physics), the present research project is aimed at:
a)clarifying the mechanisms underlying the toxicity of different nanoparticles (NP), such as carbon nanotubes or metal oxide NP, so as to yield a solid toxicologic rationale based on structure-function relationships and on relevant biological responses;
b)developing experimentally validated, reliable in vitro methods to assess NP toxicity, so as to characterize a battery of tests suitable for human health risk assessment of newly synthesized nanomaterials.
These two strictly related aims will be pursued by the Units through the achievements of intermediate endpoints:
i)the synthesis and chemical functionalization of new NPs (OUs 2 and 5);
ii)the identification of the structural determinants that influence the trans-epithelial permeability of NP across the airway epithelium (OUs1, 2, and 5);
iii)the characterization of the effects of distinct types of NP on biologically relevant cell types: airway epithelial cells (OUs1 and 5), inflammatory cells of monocyte-macrophage lineage (OUs 1 and 4), cord blood-derived stem cells differentiating into T or NK lymphocytes (OU3), human endothelial cells (OU1), human cheratinocytes (OU5), human peripheral lymphocytes (OU5);
iv)the analysis of the mechanisms of the alterations >>>

Timescale
24 months
National and international background
Nanostructured materials (NM) play a key role in most of the innovations based on nanotechnology and their production rates is expected to increase exponentially in the next few years. By tailoring the structure at the nanoscale, it is indeed possible to engineer novel materials that have entirely new physicochemical properties as compared to bulk materials. The unusual physicochemical properties of NM are attributable to the higher surface to volume ratio associated with nanoparticles (NP, i.e. particles smaller than 100 nanometres in size in at least one dimension) and the quantum effects that occur in the nanometre scale, but chemical composition, surface structure (reactivity, surface groups, inorganic or organic coatings), solubility, shape and aggregation should also be considered. Although impressive from a physicochemical point of view, the novel properties of NM raise concerns about adverse effects on biological systems, since they may favour an opportunity for enhanced uptake and interaction with several cell types and tissues [1, 2].

Most of the data available on NP concern the respiratory system where NP exert greater toxic effects than larger particles of the same substance at the same mass concentration [3]. Toxicological studies have shown that airborne ambient ultrafine particles (UFP, i.e. particulate matter smaller than 100 nm in all dimensions) produced by combustion processes [3], can induce pulmonary inflammation, oxidative stress and >>>