Ferraro, Giarita (2018) Interaction between proteins and bimetallic compounds of medicinal interest. [Tesi di dottorato]

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Abstract

Protein nanocages have attracted intense attention as drug delivery systems due to merits that include high biocompatibility, high solubility and ease of surface modification. Ferritin (Ft) nanocage has been used to encapsulate a variety of drugs and biologically active substances. Cytotoxic bimetallic compounds have been encapsulated within the Ft nanocage. Inductively plasma mass spectrometry, circular dichroism, UV-Vis absorption spectroscopy and X-ray crystallography confirm the encapsulation of these potential drugs. The structures of the adducts that these compounds form with Ft reveal that, upon encapsulation, in some cases the analysed bimetallic compounds can covalently bind the protein residues side chains , while in other cases do not interact directly with the protein. The biological activity of the drug-loaded nanocarriers has been tested: they have a cytotoxic effect on different human cancer cell lines, whereas they are significantly less cytotoxic for non-tumorigenic cells and exhibit much higher cytotoxicity than free AFt, which is basically non-toxic. The kind of cell death induced and the oxidative stress pathway activation have been deeply investigated.

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