Effects of the protein corona on liposome–liposome and liposome–cell interactions

Claudia Corbo,1,2 Roberto Molinaro,1 Francesca Taraballi,1 Naama E Toledano Furman,1 Michael B Sherman,3 Alessandro Parodi,1 Francesco Salvatore,2,4 Ennio Tasciotti1,5 1Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX, USA; 2CEINGE-Biotecnologie Avanzate s.c.a r.l., Naples, Italy; 3Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA; 4Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy; 5Department of Orthopedics, Houston Methodist Hospital, Houston, TX, USA Abstract: A thorough understanding of interactions occurring at the interface between nanocarriers and biological systems is crucial to predict and interpret their biodistribution, targeting, and efficacy, and thus design more effective drug delivery systems. Upon intravenous injection, nanoparticles are coated by a protein corona (PC). This confers a new biological identity on the particles that largely determines their biological fate. Liposomes have great pharmaceutical versatility, so, as proof of concept, their PC has recently been implicated in the mechanism and efficiency of their internalization into the cell. In an attempt to better understand the interactions between nanocarriers and biological systems, we analyzed the plasma proteins adsorbed on the surface of multicomponent liposomes. Specifically, we analyzed the physical properties and ultrastructure of liposome/PC complexes and the aggregation process that occurs when liposomes are dispersed in plasma. The results of combined confocal microscopy and flow cytometry experiments demonstrated that the PC favors liposome internalization by both macrophages and tumor cells. This work provides insights into the effects of the PC on liposomes’ physical properties and, consequently, liposome–liposome and liposome–cell interactions. Keywords: liposomes, protein corona, macrophages, cancer cell