Deferoxamine-coated mesoporous silica nanoparticles sustainably reduce iron overload in HepG2 cells. A protein corona study on plasma from hemochromatotic mice

Abstract

Elevated iron levels, as seen in hemochromatosis, can damage vital organs. Although chelators are effective at removing excess iron, they have poor pharmacokinetics, which requires repeated doses and leads to adverse side effects. Here, we report on the synthesis of mesoporous silica nanoparticles (MSN) functionalized with the clinically used chelator deferoxamine (DFO). The nanoparticles have been physicochemically characterized, demonstrating the successful grafting of the chelator and chelating features comparable to those of the free drug. The MSN-DFO have been tested in a hepatocellular carcinoma cell line (HepG2), producing an expected decline in cell viability due to intracellular iron chelation, which affects metabolic processes. Nonetheless, it has been shown that cell function is restored when the nanochelator is cleared from the cells, highlighting its overall biocompatibility. Interestingly, MSN-DFO exhibited a more gradual and prolonged iron removal process in iron-overloaded HepG2 cells than DFO did. Finally, in preparation for an in vivo administration, the protein corona formed on the MSN-DFO has been thoroughly analyzed, revealing clear differences depending on the plasma origin (wild type vs. hemochromatotic mice), highlighting the role that the protein corona fingerprint might have as a predictor of diseases, and shedding light on how this nanochelator would behave in vivo.