title: The protein corona of circulating PEGylated liposomes.
abstract: Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment.
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Palchetti
authors.affiliation: Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Colapicchioni
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 291, 00161 Rome, Italy; Department of Bioscience and Biotechnology, University of Camerino, Via Gentile III da Varano, 62032 Camerino, (MC), Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Digiacomo
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 291, 00161 Rome, Italy. Electronic address: giulio.caracciolo@uniroma1.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Caracciolo
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 291, 00161 Rome, Italy; Istituti Fisioterapici Ospitalieri, Istituto Regina Elena, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pozzi
authors.affiliation: Department of Chemistry, "Sapienza" University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Anna Laura
authors.initials: AL
authors.lastname: Capriotti
authors.affiliation: Department of Chemistry, "Sapienza" University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: La Barbera
authors.affiliation: Department of Chemistry, "Sapienza" University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Laganà
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D013058:Mass Spectrometry; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D008081:Liposomes; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000
keywords: Circulating fluids; Liposomes; PEGylation; Protein corona