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Tesi etd-04092013-193336


Thesis type
Tesi di dottorato di ricerca
Author
FABBRIZI, MARIA RITA
URN
etd-04092013-193336
Title
IN VITRO CYTOTOXIC AND GENOTOXIC EFFECTS OF DIFFERENT METAL NANOPARTICLES
Settore scientifico disciplinare
BIO/18
Corso di studi
NEUROSCIENZE E SCIENZE ENDOCRINOMETABOLICHE
Commissione
tutor Prof. Migliore, Lucia
relatore Prof. Siciliano, Gabriele
Parole chiave
  • lymphocytes
  • genotoxicity
  • aneuploidogenic
  • macrophages
Data inizio appello
15/04/2013;
Consultabilità
completa
Riassunto analitico
Several commercial nano-agents are already available for biomedical applications and many nanomedicine products are near obtaining final approval for clinical use. Besides biomedical applications, nanoparticles (NPs) are used commercially in products such as electronic components, scratch-free paint, sports equipment, cosmetics, food colour additives, and surface coatings. Hence, our exposure to nanomaterials is significant and increasing, yet there is little understanding of the unique toxicological properties of NPs and their long-term impact on human health.<br>For this reason, in this study we address the issue of cytotoxic and genotoxic effects of different metallic nanoparticles two different cell systems. Moreover, this study aim is to understand if, modifying the physicochemical characteristics of NPs, it is possible to mitigate the toxic effects they are able to induce. Thus a set of 14 different NPs was screened: 4 CuO NPs, 3 Au NPs, 4 Ag NPs and 3 SiO2 NPs. Inside every group, the NPs differ for size, shape and\or capping. The tests were performed in Raw 264.7 macrophage cells and peripheral blood lymphocytes (PBL). Macrophages are one of the principal immune effector cells that play essential roles as secretory, phagocytic and antigen-presenting cells in the immune system while PBL are present in the circulatory system and are representative of the major pathway of NPs distribution in the whole organism.<br>The results showed how NPs caused cytotoxicity and genotoxicity with different degrees of damage, often in a dose-dependent manner. The NPs set tested induced micronuclei formation and DNA damage at different levels. Oxidative stress seemed to be the most probable cause of damage, followed by the activation of apoptotic and necrotic pathways. Moreover, CuO and Au NPs induced aneuploidogenic events in cells after exposure compared to negative control. Nevertheless, it was not possible to ascribe the damage to one single physicochemical parameter of the nanoparticles, as all the characteristics seemed to act altogether in cell damaging.<br>Further investigations are required to better understand which mechanism(s) is(are) involved in the NPs toxicity and if modification in one or more physicochemical parameters could be sufficient to make NPs harmless or at least less toxic.
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