title: Stealth filaments: Polymer chain length and conformation affect the in vivo fate of PEGylated potato virus X.
abstract: Nanoparticles hold great promise for delivering medical cargos to cancerous tissues to enhance contrast and sensitivity of imaging agents or to increase specificity and efficacy of therapeutics. A growing body of data suggests that nanoparticle shape, in combination with surface chemistry, affects their in vivo fates, with elongated filaments showing enhanced tumor targeting and tissue penetration, while promoting immune evasion. The synthesis of high aspect ratio filamentous materials at the nanoscale remains challenging using synthetic routes; therefore we turned toward nature's materials, developing and studying the filamentous structures formed by the plant virus potato virus X (PVX). We recently demonstrated that PVX shows enhanced tumor homing in various preclinical models. Like other nanoparticle systems, the proteinaceous platform is cleared from circulation and tissues by the mononuclear phagocyte system (MPS). To increase bioavailability we set out to develop PEGylated stealth filaments and evaluate the effects of PEG chain length and conformation on pharmacokinetics, biodistribution, as well as potential immune and inflammatory responses. We demonstrate that PEGylation effectively reduces immune recognition while increasing pharmacokinetic profiles. Stealth filaments show reduced interaction with cells of the MPS; the protein:polymer hybrids are cleared from the body tissues within hours to days indicating biodegradability and biocompatibility. Tissue compatibility is indicated with no apparent inflammatory signaling in vivo. Tailoring PEG chain length and conformation (brush vs. mushroom) allows tuning of the pharmacokinetics, yielding long-circulating stealth filaments for applications in nanomedicine.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Mengzhi
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Ayat
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: El Sanadi
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Wen
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Edelbrock
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pokorski
authors.affiliation: Institute for Molecular Biotechnology, RWTH Aachen University, Worringer Weg 1, 52074 Aachen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Commandeur
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States.
authors.forename: George R
authors.initials: GR
authors.lastname: Dubyak
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States; Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States; Department of Radiology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States; Department of Materials Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, OH 44106, United States. Electronic address: nicole.steinmetz@case.edu.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D008422:Materials Testing; D008968:Molecular Conformation; D008970:Molecular Weight; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017863:Potexvirus / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D053769:Nanocapsules; D011092:Polyethylene Glycols
keywords: Biodistribution; Filamentous nanoparticle; PEGylation; Potato virus X; Stealth coating