title: Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles.
abstract: Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the 'protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post-injection of liposomes into CD-1 mice. The results demonstrated that a complex protein corona was formed as early as 10 min post-injection. Even though the total amount of protein adsorbed did not significantly change over time, the fluctuation of protein abundances observed indicated highly dynamic protein binding kinetics.
authors.affiliation: Nanomedicine Lab, School of Medicine, Faculty of Medical & Human Sciences and National Graphene Institute, The University of Manchester, Manchester M13 9PT, UK. kostas.kostarelos@manchester.ac.uk.
authors.forename: Marilena
authors.initials: M
authors.lastname: Hadjidemetriou
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Al-Ahmady
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000327:Adsorption; D000818:Animals; D001682:Biological Availability; D001775:Blood Circulation; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D000066970:Protein Corona / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000066970:Protein Corona; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin