Schwarz Benjamin, Douglas Trevor
Department of Chemistry, Indiana University, Bloomington, IN, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015 Sep-Oct;7(5):722-35. doi: 10.1002/wnan.1336. Epub 2015 Feb 13.
As ordered nanoscale architectures, viruses and virus-like particles (VLPs) remain unsurpassed by synthetic strategies to produce uniform and symmetric nanoparticles. Maintaining or mimicking the symmetry of pathogenic viruses, VLPs offer a ready platform for facilitating recognition, uptake, and processing by the immune system. An emerging understanding of how viruses interact with the immune system offers a means of precisely designing nanoparticles for biomedical use, both with respect to the structure of the particle as well as their ability to stimulate the immune system. Here we discuss recent advances by our group toward two parallel and complementary applications of VLPs, derived primarily from plants, bacteriophage, and nonviral sources, in biomedicine: diagnostic imaging and rational vaccine design. First we discuss advances in increasing VLP payloads of gadolinium magnetic resonance imaging (MRI) contrast agent as well as controlling the characteristics of individual gadolinium containing molecules to increase efficacy. In order to better understand the in vivo potential of VLP constructs, we then discuss the interface of protein-cages and the immune system beginning with the nonspecific innate immune system stimulation and continuing into the use of nonpathogenic VLPs as scaffolds for specific antigen presentation and control of the immune response.
作为有序的纳米级结构,病毒和病毒样颗粒(VLP)在生产均匀对称纳米颗粒的合成策略方面仍无与伦比。VLP保持或模仿致病病毒的对称性,为促进免疫系统的识别、摄取和处理提供了一个现成的平台。对病毒如何与免疫系统相互作用的新认识为精确设计用于生物医学的纳米颗粒提供了一种方法,这涉及颗粒的结构及其刺激免疫系统的能力。在这里,我们讨论了我们小组在VLP的两个平行且互补的应用方面的最新进展,这些VLP主要来源于植物、噬菌体和非病毒来源,应用于生物医学领域:诊断成像和合理的疫苗设计。首先,我们讨论了增加钆磁共振成像(MRI)造影剂的VLP负载量以及控制单个含钆分子的特性以提高疗效方面的进展。为了更好地理解VLP构建体的体内潜力,我们接着讨论蛋白质笼与免疫系统的界面,从非特异性先天性免疫系统刺激开始,一直到使用非致病性VLP作为特定抗原呈递和免疫反应控制的支架。