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A possible turning point in drug delivery has been recently reached: the protein shell, which covers nanocarriers in vivo, can be used for targeting. Here, we show that nanoparticles can acquire a selective targeting capability with a protein corona adsorbed on the surface. We demonstrate that lipid particles made of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and DNA, upon interaction with human plasma components, spontaneously become coated with vitronectin that promotes efficient uptake in cancer cells expressing high levels of the vitronectin α_νβ₃ integrin receptor.