Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo
| Autor: | Giuseppe Destito, Marianne Manchester, Chris S. Rae, M. G. Finn, Pratik Singh, Kent G. Osborn, Robert M. Yeh, Duane E. Prasuhn |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Biodistribution Pathology medicine.medical_specialty Comovirus Molecular Conformation Pharmaceutical Science Spleen Virus Article Flow cytometry Mice In vivo Heterocyclic Compounds medicine Organometallic Compounds Animals Terbium Drug Carriers Mice Inbred BALB C biology medicine.diagnostic_test Chemistry Cowpea mosaic virus Virion biology.organism_classification medicine.disease Molecular biology Cellular infiltration medicine.anatomical_structure Liver Spectrophotometry Toxicity Injections Intravenous Nanoparticles |
| Popis: | Virus-based nanoparticles (VNPs) from a variety of sources are being developed for biomedical and nanotechnology applications that include tissue targeting and drug delivery. However, the fate of most of those particles in vivo has not been investigated. Cowpea mosaic virus (CPMV), a plant comovirus, has been found to be amenable to the attachment of a variety of molecules to its coat protein, as well as to modification of the coat protein sequence by genetic means. We report here the results of studies of the bio-distribution, toxicology, and pathology of CPMV in mice. Plasma clearance and tissue biodistribution were measured using CPMV particles derivatized with lanthanide metal complexes. CPMV particles were cleared rapidly from plasma, falling to undetectable levels within 20 minutes. By 30 minutes the majority of the injected VNPs were trapped in the liver and to a lesser extent the spleen with undetectable amounts in other tissues. At doses of 1 mg, 10 mg and 100 mg per kg body weight, no toxicity was noted and the mice appeared to be normal. Hematology was essentially normal, although with the highest dose examined, the mice were somewhat leukopenic with relative decreases in both neutrophils and lymphocytes. Histological examination of spleen showed cellular infiltration, which upon flow cytometry analyses revealed elevated B lymphocytes on the first day following virus administration that subsequently subsided. Microscopic evaluation of various other tissues revealed a lack of apparent tissue degeneration or necrosis. Overall, CPMV appears to be a safe and non-toxic platform for in vivo biomedical applications. |
| Databáze: | OpenAIRE |
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