Singh Pratik, Prasuhn Duane, Yeh Robert M, Destito Giuseppe, Rae Chris S, Osborn Kent, Finn M G, Manchester Marianne
Center for Integrative Molecular Biosciences, The Scripps Research Institute, La Jolla, California 92037, USA.
J Control Release. 2007 Jul 16;120(1-2):41-50. doi: 10.1016/j.jconrel.2007.04.003. Epub 2007 Apr 13.
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 min. By 30 min 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 the 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.
来自多种来源的基于病毒的纳米颗粒（VNPs）正被开发用于生物医学和纳米技术应用，包括组织靶向和药物递送。然而，这些颗粒在体内的命运大多尚未得到研究。豇豆花叶病毒（CPMV）是一种植物豇豆花叶病毒，已被发现适合于将多种分子附着于其衣壳蛋白，以及通过基因手段修饰衣壳蛋白序列。我们在此报告CPMV在小鼠体内的生物分布、毒理学和病理学研究结果。使用镧系金属络合物衍生化的CPMV颗粒测量血浆清除率和组织生物分布。CPMV颗粒从血浆中迅速清除，在20分钟内降至检测不到的水平。到30分钟时，大多数注射的VNPs被困在肝脏中，脾脏中的含量较少，其他组织中含量检测不到。在每千克体重1毫克、10毫克和100毫克的剂量下，未观察到毒性，小鼠看起来正常。血液学基本正常，尽管在检测的最高剂量下，小鼠出现了一定程度的白细胞减少，中性粒细胞和淋巴细胞均相对减少。脾脏的组织学检查显示有细胞浸润，流式细胞术分析显示在病毒给药后的第一天B淋巴细胞升高，随后消退。对其他各种组织的显微镜评估显示没有明显的组织变性或坏死。总体而言,CPMV似乎是一种用于体内生物医学应用的安全无毒平台。
