title: Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio.
abstract: Nanoparticle-based technologies, including platforms derived from plant viruses, hold great promise for targeting and delivering cancer therapeutics to solid tumors by overcoming dose-limiting toxicities associated with chemotherapies. A growing body of data indicates advantageous margination and penetration properties of high aspect-ratio nanoparticles, which enhance payload delivery, resulting in increased efficacy. Our lab has demonstrated that elongated rod-shaped and filamentous macromolecular nucleoprotein assemblies from plant viruses have higher tissue diffusion rates than spherical particles. In this study, we developed a mathematical model to quantify diffusion and uptake of tobacco mosaic virus (TMV) in a spheroid system approximating a capillary-free segment of a solid tumor. Model simulations predict TMV concentration distribution with time in a tumor spheroid for different sizes and cell densities. From simulations of TMV concentration distribution, we can quantify the effect of TMV aspect ratio (e.g., nanorod length-to-width) with and without cellular uptake by modulated surface chemistry. This theoretical analysis can be applied to other viral or nonviral delivery systems to complement the experimental development of the next generation of nanotherapeutics.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering , Cleveland, Ohio 44106, United States.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Chariou
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering , Cleveland, Ohio 44106, United States.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Radiology, Case Western Reserve University School of Engineering , Cleveland, Ohio 44106, United States.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pokorski
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering , Cleveland, Ohio 44106, United States.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Saidel
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering , Cleveland, Ohio 44106, United States.|Department of Radiology, Case Western Reserve University School of Engineering , Cleveland, Ohio 44106, United States.|Department of Materials Science and Engineering, Case Western Reserve University School of Engineering , Cleveland, Ohio 44106, United States.|Department of Macromolecular Science and Engineering, Case Western Reserve University School of Engineering , Cleveland, Ohio 44106, United States.|Department of Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D001692:Biological Transport; D002452:Cell Count; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004058:Diffusion; D004337:Drug Carriers / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D043942:Nanotubes; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D013499:Surface Properties; D014018:Tissue Distribution; D014027:Tobacco Mosaic Virus / Q000378:metabolism*
chemical_list: D004337:Drug Carriers