Department of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 44 Prague 2, Czech Republic.
Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
Bioconjug Chem. 2020 May 20;31(5):1575-1585. doi: 10.1021/acs.bioconjchem.0c00240. Epub 2020 May 8.
Protein corona formation has been regarded as an obstacle to developing diagnostic and therapeutic nanoparticles for applications. Serum proteins that assemble around nanoparticles can hinder their targeting efficiency. Virus-based nanoparticles should be naturally predisposed to evade such barriers in host organisms. Here, we demonstrate that virus-like particles derived from mouse polyomavirus do not form a rich protein corona. These particles can be efficiently targeted to cells that overproduce transferrin receptors, e.g., cancer cells, by conjugating transferrin to the particle surface. In this study, we provide evidence that the interaction of virus-like particles with their newly assigned target receptor is not obstructed by serum proteins. The particles enter target cells via a clathrin-dependent endocytic pathway that is not naturally used by the virus. Our results support the notion that the natural properties of virus-like particles make them well-suited for development of nanosized theranostic tools resistant to detargeting by protein coronas.
蛋白质冠形成一直被认为是开发用于诊断和治疗的纳米粒子的障碍。在纳米粒子周围组装的血清蛋白会阻碍它们的靶向效率。基于病毒的纳米粒子应该能够自然地逃避宿主生物中的这种障碍。在这里，我们证明了源自小鼠多瘤病毒的类病毒颗粒不会形成丰富的蛋白质冠。通过将转铁蛋白连接到颗粒表面，可以将这些颗粒有效地靶向转铁蛋白受体过度表达的细胞，例如癌细胞。在这项研究中，我们提供的证据表明，类病毒颗粒与其新指定的靶受体的相互作用不受血清蛋白的阻碍。颗粒通过网格蛋白依赖性内吞途径进入靶细胞，而该途径不是病毒天然使用的途径。我们的结果支持这样的观点，即类病毒颗粒的天然特性使它们非常适合开发纳米级治疗诊断工具，这些工具能够抵抗由蛋白质冠引起的脱靶作用。
