title: Biodistribution, pharmacokinetics, and blood compatibility of native and PEGylated tobacco mosaic virus nano-rods and -spheres in mice.
abstract: Understanding the pharmacokinetics, blood compatibility, biodistribution and clearance properties of nanoparticles is of great importance to their translation to clinical application. In this paper we report the biodistribution and pharmacokinetic properties of tobacco mosaic virus (TMV) in the forms of 300×18nm(2) rods and 54nm-sized spheres. The availability of rods and spheres made of the same protein provides a unique scaffold to study the effect of nanoparticle shape on in vivo fate. For enhanced biocompatibility, we also considered a PEGylated formulation. Overall, the versions of nanoparticles exhibited comparable in vivo profiles; a few differences were noted: data indicate that rods circulate longer than spheres, illustrating the effect that shape plays on circulation. Also, PEGylation increased circulation times. We found that macrophages in the liver and spleen cleared the TMV rods and spheres from circulation. In the spleen, the viral nanoparticles trafficked through the marginal zone before eventually co-localizing in B-cell follicles. TMV rods and spheres were cleared from the liver and spleen within days with no apparent changes in histology, it was noted that spheres are more rapidly cleared from tissues compared to rods. Further, blood biocompatibility was supported, as none of the formulations induced clotting or hemolysis. This work lays the foundation for further application and tailoring of TMV for biomedical applications.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bruckman
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Randolph
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: VanMeter
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hern
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Shoffstall
authors.affiliation: Department of Chemistry, Williams College, 47 Lab Campus Drive, Williamstown, MA 01267, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Taurog
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Radiology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Materials Science and Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Macromolecular Science and Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: nicole.steinmetz@case.edu.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000821:virology; D014018:Tissue Distribution; D014027:Tobacco Mosaic Virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
chemical_list: D011092:Polyethylene Glycols
keywords: Biodistribution; Blood compatibility; Nanoparticle shape; PEGylation; Pharmacokinetics; Tobacco mosaic virus; Viral nanoparticle