Cancer cell targeting of lipid gene vectors by protein corona

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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.

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Journal: TechConnect Briefs
Volume: 3, Nanotechnology 2012: Bio Sensors, Instruments, Medical, Environment and Energy (Volume 3)
Published: June 18, 2012
Pages: 354 - 357
Industry sectors: Advanced Materials & Manufacturing | Energy & Sustainability
Topic: Environmental Health & Safety of Nanomaterials
ISBN: 978-1-4665-6276-9