(A) Following exposure to plasma proteins, liposomes’ surface is decorated by a biomolecular corona (BC), which depends on several factors such liposome’ physiochemical properties (i.e. surface chemistry, size, charge etc.), protein source (e.g. human plasma vs. mouse plasma) and environmental factors (i.e. temperature, pH, etc.). To the sake of clarify, we underline that proteins cover liposome’ surface entirely, but, for simplicity of representation, we left the liposome surface only partly decorated by plasma proteins. (B) When particles are given to HeLa cells, they are efficiently internalized with cellular uptake being higher than 90% as quantified by flow cytometry. Despite similar levels of cellular uptake, BC promotes a neat switch of cell entry mechanism of liposomes, from macropinocytosis to clathrin-dependent endocytosis (C). BC has a major impact on the intracellular dynamics of liposomes. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses.