Supervisors info:
Αλέξανδρος Γεωργακίλας, Αναπληρωτής Καθηγητής, Σχολή Εφαρμοσμένων Μαθηματικών και Φυσικών Επιστημών, Εθνικό Μετσόβιο Πολυτεχνείο
Κωνσταντίνος Βοργιάς,Καθηγητής, Τμήμα Βιολογίας, Εθνικό Καποδιστριακό Πανεπιστήμιο Αθηνών
Παντελής Μπάγκος, Καθηγητής, Τμήμα Πληροφορικής με Εφαρμογές στη Βιοϊατρική, Πανεπιστήμιο Θεσσαλίας
Summary:
Nanotechology is a science counting less than fifty years. This science has allowed humans to manufacture and study materials in the smallest of dimensions. When dimensions become smaller than 100nm, matter behaves differently, and its properties and behavior change as quantum laws prevail. In the current study, firstly there is a review of the most recent achievements on a biological and clinical level using nanotechnology, which were accomplished by making use of gold and silver nanoparticles’ properties. Following is a combined study of DNA microarrays data, with the aim of finding possible nanoparticle activated mechanisms or biological phenomena correlated to nanoparticle exposure.
The method followed was firstly to find and pick the raw data. For that reason, GEO repository was used and the data from the series GSE55349, GSE62253 and GSE84982 was selected, mainly because of their matching cell type matching (Caco-2) and crude nanoparticles. As far as date analysis in concerned, a Kruskal-Wallis algorithm was used to find possible statistically important differentially expressed genes, as well as Paired-Wilcoxon comparisons and Benjamini corrections. Then, by using the InSyBio platform, a differential expression analysis was carried out by using non-parametrical (Wilcoxon Rank Sum test) and parametrical methods (Student T-test). The final gene selection was made by fold change limitation. Up next was the functional annotation of DEGs by using DAVID, miRNA binding sites checking and construction of protein-protein interaction networks of the most differentially expressed genes by using STRING.
The analysis results for the effects of nanoparticles on Caco-2 cells seem to be affected by the material type, the size and the sampling time. In addition, the main effect of nanoparticles seems to be the upregulation of genes correlated to negative cell growth regulation, activation of response mechanisms to oxidative stress and cell response to metals. Moreover, many of the upregulated genes seem to belong to Nrf2 transcription factor mediated signaling cascades.
Furthermore, no strictly nanoparticle correlated mechanisms were discovered, because silver seems to affect cells the same, whether in nanoparticle or ionic form. When comparing the bioreactivity of the two metals (gold, silver), the results suggest that while gold seems to be biologically inert even when inside the cell if it is in the form of bigger nanoparticles, silver does not seem to change its bioreactivity according to particle size, while on the same time seems to affect the cells by being mostly outside, as its cellular uptake is very low.
To conclude, the many variables that are different between the three selected data series, such as the platform, the cell differentiation and the sampling time, render such kind of analysis difficult and more often than not inaccurate. On this basis, the design of new studies is deemed indispensable and necessary, as well as the carrying out of further analysis for the accurate clarification of nanoparticles’ effects on cells, due to their material, size and underlying mechanisms behind each effect.
Keywords:
gold nanoparticles, silver nanoparticles, caco-2 cells, differential expression of genes, bioinformatics, microarray analysis, biological applications, clinical applications, AuNPs, GNPs, AgNPs
