Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles

Sci Rep. 2016 Feb 24:6:21803. doi: 10.1038/srep21803.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism*
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Evaluation, Preclinical
  • HeLa Cells
  • Humans
  • Melanoma, Experimental
  • Mice
  • Mosaic Viruses
  • Protein Multimerization
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sesbania / virology
  • Staphylococcal Protein A / chemistry
  • Staphylococcal Protein A / metabolism
  • Virion

Substances

  • Antibodies, Monoclonal
  • Drug Carriers
  • Recombinant Fusion Proteins
  • Staphylococcal Protein A