title: Serum albumin 'camouflage' of plant virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics.
abstract: Plant virus-based nanoparticles (VNPs) are a novel class of nanocarriers with unique potential for biomedical applications. VNPs have many advantageous properties such as ease of manufacture and high degree of quality control. Their biocompatibility and biodegradability make them an attractive alternative to synthetic nanoparticles (NPs). Nevertheless, as with synthetic NPs, to be successful in drug delivery or imaging, the carriers need to overcome several biological barriers including innate immune recognition. Plasma opsonization can tag (V)NPs for clearance by the mononuclear phagocyte system (MPS), resulting in shortened circulation half lives and non-specific sequestration in non-targeted organs. PEG coatings have been traditionally used to 'shield' nanocarriers from immune surveillance. However, due to broad use of PEG in cosmetics and other industries, the prevalence of anti-PEG antibodies has been reported, which may limit the utility of PEGylation in nanomedicine. Alternative strategies are needed to tailor the in vivo properties of (plant virus-based) nanocarriers. We demonstrate the use of serum albumin (SA) as a viable alternative. SA conjugation to tobacco mosaic virus (TMV)-based nanocarriers results in a 'camouflage' effect more effective than PEG coatings. SA-'camouflaged' TMV particles exhibit decreased antibody recognition, as well as enhanced pharmacokinetics in a Balb/C mouse model. Therefore, SA-coatings may provide an alternative and improved coating technique to yield (plant virus-based) NPs with improved in vivo properties enhancing drug delivery and molecular imaging.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Pitek
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Slater A
authors.initials: SA
authors.lastname: Jameson
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Veliz
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.affiliation: 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. Electronic address: nicole.steinmetz@case.edu.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000821:virology; D011092:Polyethylene Glycols / Q000737:chemistry; D000067996:RAW 264.7 Cells; D012709:Serum Albumin / Q000737:chemistry* / Q000276:immunology; D014026:Nicotiana / Q000821:virology; D014027:Tobacco Mosaic Virus / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D012709:Serum Albumin; D011092:Polyethylene Glycols
keywords: Drug delivery; Nanomedicine; Pharmacokinetics; Stealth and camouflage; Tobacco mosaic virus (TMV)