Biobehavior in Normal and Tumor-Bearing Mice of Tobacco Mosaic Virus

Abstract

Viral nanoparticles (VNPs) have shown great potential as platforms for biomedical applications. Before using VNPs for further biomedical applications, it is important to clarify their biological behavior in vivo, which is rare for rod-like VNPs. In this paper, a study of tobacco mosaic virus (TMV), a typical rod-like VNP, is performed on blood clearance kinetics, biodistributions in both normal and tumor-bearing mice, histopathology and cytotoxicity. TMV was radiolabeled with (125)I using Iodogen method for in vivo quantitative analysis and imaging purpose. In the normal mice, the accumulation of TMV in the immune system led to a rapid blood clearance. The uptake of TMVs in the liver was less than that in the spleen, which is opposite to the results observed in the case of spherical VNPs. No signs of overt toxicity were observed in examined tissues according to the results of histological analysis. In addition, similar biodistribution patterns were observed in U87MG tumor-bearing mice.

Plant virus incorporated hydrogels as scaffolds for tissue engineering possess low immunogenicity in vivo

“…The spleen acts as a blood filter in the body, removing and replacing worn out red blood cells, and it is the center of activity in the RES system. Since TMV particles were eliminated from the blood circulation by the RES, the accumulation of excess amount of TMV may cause spleen enlargement and damage . However, normal weight and morphology of the spleen observed from each mouse after the sacrifice indicated that there were no chronic and/or major inflammatory and toxicity reactions in the RES that could cause the spleen enlargement in any group of animals.…”

“…In vivo properties, especially any potential toxic effects, need to be taken into account, when developing novel materials for biomedical applications. There have been many studies that reported in vivo characterization including biodistribution and toxicity of different types of viral nanoparticles used in biomedicine . For example, spherical plant viruses, cowpea mosaic virus (CPMV), and cowpea chlorotic mottle virus (CCMV), as well as filamentous bacteriophage M13, showed broad biodistribution throughout the body, predominantly in the liver and the spleen.…”

“…The study demonstrated that radio‐iodinated TMV was accumulated mostly in the spleen and the liver of BALB/c mice and U87MG tumor‐bearing mice with no overt toxicity. About 97% of TMV particles were eliminated from the blood circulation by the reticuloendothelial system (RES) within 40 min after intravenous (IV) administration of ∼1 μg TMV per animal . Liver and spleen are parts of the RES that play a critical role in removing antigens, including structured proteinaceous nanoparticles, from circulation through mononuclear phagocyte system .…”

“…Moreover, PEGylation of TMV could create the stealth layer shielding TMV from recognition of RES leading to the longer circulation of the nanoparticle in blood stream . However, the immune responses for TMV were not addressed . These studies suggested that, even though, the animal's physiologic system recognizes the viral nanoparticles as foreign bodies, these do not necessarily reflect the systemic toxicity.…”

“…There have been many studies that reported in vivo characterization including biodistribution and toxicity of different types of viral nanoparticles used in biomedicine. [15][16][17][18][19][20] For example, spherical plant viruses, cowpea mosaic virus (CPMV), and cowpea chlorotic mottle virus (CCMV), as well as filamentous bacteriophage M13, showed broad biodistribution throughout the body, predominantly in the liver and the spleen. However, no in vivo systemic toxicity was observed.…”