Cancer cell targeting of lipid gene vectors by protein corona

G. Caracciolo, D. Pozzi, A.L. Capriotti, C. Cavaliere, F. Cardarelli, A. Bifone, G. Bardi, F. Salomone, A. Laganà
Sapienza University of Rome, IT

Keywords: protein corona, cancer cells, gene vectors, lipid, cationic liposomes


We investigated the compositional evolution of the protein corona of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) cationic liposomes (CLs) that efficiently deliver DNA in a wide variety of cell lines as a function of increasing human plasma (HP) concentration. We applied liquid chromatography-tandem mass spectrometry to quantitatively identify the proteins adsorbed on DOTAP CLs at 2.5% HP (mimicking the conditions of in vitro experiments) and 50% HP (mimicking the conditions of in vivo experiments) and we observed that, when passing from 2.5% to 50% plasma concentration, fibrinogen is displaced by proteins such as vitronectin and complement C3 proteins. Vitronectin is a major ligand for the vitronectin receptor αVβ3 or αVβ5 integrin, which are overexpressed in some tumor cell lines. Thus, we asked whether the adsorbed protein corona at 50% HP could dictate a selective access to cells expressing vitronectin receptor, that are ανβ3 and ανβ5 integrins. We peformed Confocal Laser Scanning Microscopy and Fluorescence Activated Cell Sorting experiments on metastatic MDA-MB-435 cells that express high level of ανβ3 and ανβ5 integrin and non-metastatic MCF7 that do not express ανβ3 and ανβ5 integrins. We found that DOTAP CLs dressed by protein corona are more efficiently internalized within metastatic MDA-MB-435 cells than naked DOTAP CLs.