title: In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles.
abstract: The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (IgG) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of antibody-conjugated liposomes; however, the in vivo corona formation did not lead to complete ablation of their targeting capability.
authors.forename: Marilena
authors.initials: M
authors.lastname: Hadjidemetriou
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Al-Ahmady
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Mazza
authors.forename: Richard F
authors.initials: RF
authors.lastname: Collins
authors.affiliation: Centre For BioNano Interactions (CBNI), School of Chemistry and Chemical Biology, University College Dublin , Belfield, Dublin 4, Ireland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dawson
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000327:Adsorption; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry*; D007275:Injections, Intravenous; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D001798:Blood Proteins; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C506643:liposomal doxorubicin; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
keywords: Doxil; fibrillation; nanomedicine; nanoparticle; nanotoxicology; protein corona