Biodistribution, pharmacokinetics, and blood compatibility of native and PEGylated tobacco mosaic virus nano-rods and -spheres in mice.

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.

Shape matters: the diffusion rates of TMV rods and CPMV icosahedrons in a spheroid model of extracellular matrix are distinct.

Nanomaterial-based carrier systems hold great promise to deliver therapies with increased efficacy and reduced side effects. While the state-of-the-art carrier system is a sphere, recent data indicate that elongated rods and filaments have advantageous flow and margination properties, resulting in enhanced vascular targeting and tumor homing. Here, we report on the distinct diffusion rates of two bio-inspired carrier systems: 30 nm-sized spherical cowpea mosaic virus (CPMV) and 300×18 nm-sized tobacco mosaic virus (TMV) with a tubular structure, using a spheroid model of the tumor microenvironment and fluorescent imaging.

Tobacco mosaic virus rods and spheres as supramolecular high-relaxivity MRI contrast agents.

To compensate for the low sensitivity of magnetic resonance imaging (MRI), nanoparticles have been developed to deliver high payloads of contrast agents to sites of disease. Here, we report the development of supramolecular MRI contrast agents using the plant viral nanoparticle tobacco mosaic virus (TMV). Rod-shaped TMV nanoparticles measuring 300×18 nm were loaded with up to 3,500 or 2,000 chelated paramagnetic gadolinium (III) ions selectively at the interior (iGd-TMV) or exterior (eGd-TMV) surface, respectively. Spatial control is achieved through targeting either tyrosine or carboxylic acid side chains on the solvent exposed exterior or interior TMV surface. The ionic T1 relaxivity per Gd ion (at 60 MHz) increases from 4.9 mM-1s-1 for free Gd(DOTA) to 18.4 mM-1s-1 for eGd-TMV and 10.7 mM-1s-1 for iGd-TMV. This equates to T1 values of ~ 30,000 mM-1s-1 and ~ 35,000 mM-1s-1 per eGd-TMV and iGd-TMV nanoparticle. Further, we show that interior-labeled TMV rods can undergo thermal transition to form 170 nm-sized spherical nanoparticles containing ~ 25,000 Gd chelates and a per particle relaxivity of almost 400,000 mM-1s-1 (15.2 mM-1s-1 per Gd). This work lays the foundation for the use of TMV as a contrast agent for MRI.

Probability distributions for showering and bathing water-use behavior for various U.S. subpopulations.

It has been shown that bathroom-type water uses dominate personal exposure to water-borne contaminants in the home. Therefore, in assessing exposure of specific population groups to the contaminants in the water, understanding population water-use behavior for bathroom activities as a function of demographic characteristics is vital to realistic exposure estimates. In this article, shower and bath frequencies and durations are analyzed, presented, and compared for various demographic groups derived from analyses of the National Human Activities Pattern Survey (NHAPS) database and the Residential End Uses of Water Study (REUWS) database as well as from a review of current literature. Analysis showed that age and level of education significantly influenced shower and bath frequency and duration. The frequency of showering and bathing reported in NHAPS agreed reasonably well with previous studies; however, durations of these events were found to be significantly longer. Showering frequency reported in REUWS was slightly less than that reported for NHAPS; however, durations of showers reported in REUWS are consistent with other studies. After considering the strengths and weaknesses of each data set and comparing their results to previous studies, it is concluded that NHAPS provides more reliable frequency data, while REUWS provides more reliable duration data. The shower- and bath-use behavior parameters recommended in this article can aid modelers in appropriately specifying water-use behavior as a function of demographic group in order to conduct reasonable assessments of exposure to contaminants that enter the home via the water supply.