title: The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates.
abstract: Biomolecules in bodily fluids such as plasma can adsorb to the surface of nanoparticles and influence their biological properties. This phenomenon, known as the protein corona, is well established in the field of synthetic nanotechnology but has not been described in the context of plant virus nanoparticles (VNPs). The interaction between VNPs derived from Tobacco mosaic virus (TMV) and plasma proteins is investigated, and it is found that the VNP protein corona is significantly less abundant compared to the corona of synthetic particles. The formed corona is dominated by complement proteins and immunoglobulins, the binding of which can be reduced by PEGylating the VNP surface. The impact of the VNP protein corona on molecular recognition and cell targeting in the context of cancer and thrombosis is investigated. A library of functionalized TMV rods with polyethylene glycol (PEG) and peptide ligands targeting integrins or fibrin(ogen) show different dispersion properties, cellular interactions, and in vivo fates depending on the properties of the protein corona, influencing target specificity, and non-specific scavenging by macrophages. Our results provide insight into the in vivo properties of VNPs and suggest that the protein corona effect should be considered during the development of efficacious, targeted VNP formulations.
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Andrzej S
authors: AS
authors: Pitek
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Amy M
authors: AM
authors: Wen
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Sourabh
authors: S
authors: Shukla
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.|Department of Radiology, Case Western Reserve University, Cleveland, OH, 44106, USA.|Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.|Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Nicole F
authors: NF
authors: Steinmetz
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D000066970:Protein Corona / Q000737:chemistry*; D014018:Tissue Distribution; D014027:Tobacco Mosaic Virus / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D009842:Oligopeptides; D000066970:Protein Corona; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid
keywords: CREKA; GPRPP; RGD; drug/contrast agent delivery; nanomedicine