Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Department of Chemistry, Williams College, 47 Lab Campus Drive, Williamstown, MA 01267, USA.
Virology. 2014 Jan 20;449:163-73. doi: 10.1016/j.virol.2013.10.035. Epub 2013 Dec 5.
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 300×18nm(2) rods and 54nm-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.
了解纳米粒子的药代动力学、血液相容性、生物分布和清除特性对于将其转化为临床应用非常重要。在本文中,我们报告了烟草花叶病毒(TMV)在 300×18nm(2)棒和 54nm 大小的球体形式下的生物分布和药代动力学特性。由相同蛋白质制成的棒和球体的可用性为研究纳米颗粒形状对体内命运的影响提供了独特的支架。为了提高生物相容性,我们还考虑了一种聚乙二醇化的配方。总的来说,纳米粒子的各个版本表现出相似的体内特征;有一些差异值得注意:数据表明,棒在体内循环的时间比球体长,这说明了形状对循环的影响。此外,聚乙二醇化增加了循环时间。我们发现肝脏和脾脏中的巨噬细胞从循环中清除 TMV 棒和球体。在脾脏中,病毒纳米颗粒通过边缘区运输,最终在 B 细胞滤泡中聚集。TMV 棒和球体在几天内从肝脏和脾脏中清除,组织学没有明显变化,但注意到与棒相比,球体从组织中更快地清除。此外,血液生物相容性得到支持,因为没有一种制剂会引起凝血或溶血。这项工作为进一步应用和定制 TMV 用于生物医学应用奠定了基础。