Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Abstract

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.

Plasma Clearance of Bacteriophage Qβ Particles as a Function of Surface Charge

“…Therefore, samples do not degrade upon storage and can be re-assayed at any time. (8) No radioactivity is used, to the benefit of both safety and convenience.…”

Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

“…Several investigations utilizing in vivo imaging and histopathologic surveys are presently being conducted to determine the biological properties, biodistribution, and toxicity of different drug carriers or nanodevices. [1][2][3] Potentially suitable nanocarriers are widely variable, ranging from nanoscale biologically derived or artificial virus-like particles to engineered (up to micron-sized) particles; consequently, they have a highly variable biological impact submit your manuscript | www.dovepress.com…”

“…Polymer-based nanoparticles conjugated to fluorescent markers and targeting antibodies have been used with fewer reported toxic side effects compared to those derived from biological systems. 2 Loading of SPION into other constructed particles, such as liposomes, may modify particle size and hence affect biodistribution and elimination of the contrast agent and the drug delivery device. 38 Large gas-filled microbubbles provide additional ultrasound contrast.…”

Bioinspired optical antennas: gold plant viruses

“…Even with their simple composition, viruses have evolved to attain the capability to enter a cell and utilize the host to replicate their genomes, re-assemble, and disseminate their progeny. Over the past century, these processes have been extensively studied to achieve better control of viral diseases, especially in plants; moreover, at present, attempts are being made in nanotechnology and biotechnology to engineer viruses for diagnostic/ therapeutic applications, [13][14][15][16][17] nanomaterial synthesis, 18,19 protein recombination, 20,21 energy harvesting, 22,23 and even the fabrication of electronic components. 24,25 These new approaches to virus engineering involve eliminating the viral disease-causing characteristics or, more accurately, incorporating only the inherent circulatory and targeting capabilities of viruses into the design of applications.…”