Abraham Ambily, Natraj Usha, Karande Anjali A, Gulati Ashutosh, Murthy Mathur R N, Murugesan Sathyabalan, Mukunda Pavithra, Savithri Handanahal S
Department of Biochemistry, Indian Institute of Science, Karnataka, India.
Molecular Biophysics Unit, Indian Institute of Science, Karnataka, India.
Sci Rep. 2016 Feb 24;6:21803. doi: 10.1038/srep21803.
The therapeutic potential of antibodies has not been fully exploited as they fail to cross cell membrane. In this article, we have tested the possibility of using plant virus based nanoparticles for intracellular delivery of antibodies. For this purpose, Sesbania mosaic virus coat protein (CP) was genetically engineered with the B domain of Staphylococcus aureus protein A (SpA) at the βH-βI loop, to generate SeMV loop B (SLB), which self-assembled to virus like particles (VLPs) with 43 times higher affinity towards antibodies. CP and SLB could internalize into various types of mammalian cells and SLB could efficiently deliver three different monoclonal antibodies-D6F10 (targeting abrin), anti-α-tubulin (targeting intracellular tubulin) and Herclon (against HER2 receptor) inside the cells. Such a mode of delivery was much more effective than antibodies alone treatment. These results highlight the potential of SLB as a universal nanocarrier for intracellular delivery of antibodies.
抗体的治疗潜力尚未得到充分发挥，因为它们无法穿过细胞膜。在本文中，我们测试了使用基于植物病毒的纳米颗粒进行抗体细胞内递送的可能性。为此，将田菁花叶病毒外壳蛋白（CP）在βH-βI环处与金黄色葡萄球菌蛋白A（SpA）的B结构域进行基因工程改造，生成田菁花叶病毒环B（SLB），其自组装成病毒样颗粒（VLP），对抗体的亲和力高43倍。CP和SLB可以内化到各种类型的哺乳动物细胞中，并且SLB可以有效地将三种不同的单克隆抗体——D6F10（靶向相思子毒素）、抗α-微管蛋白（靶向细胞内微管蛋白）和赫克隆（针对HER2受体）递送到细胞内。这种递送方式比单独使用抗体治疗更有效。这些结果突出了SLB作为抗体细胞内递送通用纳米载体的潜力。
