Acido (R)-9-idrossiottadecanoico veicolato da nanoparticelle proteiche: sintesi, caratterizzazione e valutazione dell’attività biologica

Busi, Alberto (2017) Acido (R)-9-idrossiottadecanoico veicolato da nanoparticelle proteiche: sintesi, caratterizzazione e valutazione dell’attività biologica. [Laurea magistrale], Università di Bologna, Corso di Studio in Chimica industriale [LM-DM270]
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This work describes the preparation and characterization of protein nanoparticles loaded with (R)-9-hydroxystearic acid, (R)-9-HSA. This fatty acid is an endogenous product of lipid metabolism that acts as histone deacetylase 1 inhibitor and exerts anti-proliferative activity by arresting colon cancer cells (HT29) growth in G0/G1 phase. The formation of nanoparticles was induced by hydrophobic interactions between (R)-9-HSA and the hydrophobic protein domains, affording water-stable nanoparticles with no need of toxic cross-linking agents. Nanoparticles were characterized in terms of hydrodynamic diameter, surface charge, morphology and thermogravimetric behavior. The controlled release of (R)-9-HSA from nanoparticles was determined at 37°C and at different pH values by internal standard method with quantitative 1H-NMR spectroscopy (qNMR). The in vitro evaluation of nanoparticles uptake and cytoxicity was performed on human colorectal adenocarcinoma cells (HT29). Collected data show that the activity of (R)-9-HSA as free or loaded onto nanoparticles is similar in terms of anti-proliferative effect; however, some significant differences were observed in the cell cycle analysis, showing that while free (R)-9-HSA causes a growth arrest in the G0/G phase, it induces a S phase arrest when loaded on nanoparticles. In summary, protein nanoparticles loaded with (R)-9-HSA, described here for the first time, represent an effective tool against colon cancer cells proliferation. Additional studies are ongoing to better elucidate the underpinning biochemical mechanism of action of our newly developed delivery system.

Tipologia del documento
Tesi di laurea (Laurea magistrale)
Autore della tesi
Busi, Alberto
Relatore della tesi
Correlatore della tesi
Corso di studio
Ordinamento Cds
Parole chiave
(R)-9-hydroxystearic acid protein nanoparticles HDACi nanomedicine HT29
Data di discussione della Tesi
24 Marzo 2017

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