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

- TMV particles exhibit two‐phase decay pharmacokinetics, with rods circulating longer than spheres.
- TMV particles are cleared from circulation by the reticuloendothelial system.
- TMV particles are cleared from the liver and spleen within days.
- TMV particles show blood biocompatibility and no apparent changes in tissue histology.

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 300×18 nm2 rods and 54 nm-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.

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