Nanocarrier mediated intracellular delivery of neutralizing antibodies for the management of abrin lethality

Abstract

Abrin is a highly lethal ribosome-inactivating protein of high relevance in bio-warfare. Neutralizing antibodies to abrin reported so far afford protection in a very small window with no rescue observed post-abrin exposure. The utility of the most specific mode of defense against abrin poisoning is thus undermined. We proposed that intracellular delivery of antibodies which otherwise lack the ability to enter cells would increase the therapeutic potential. Towards this, we analyzed the use of silica nanoparticles and chimeric Sesbania mosaic virus-like particles in delivering antibodies inside cells. The antibody-nanocarrier conjugate was found to be effective in protecting cells from abrin-mediated toxicity when administered as long as 9 h prior and up to 1 h post abrin exposure. These results highlight the potential of nanocarrier-based intracellular delivery of neutralizing antibodies in widening the therapeutic window for prophylaxis and to some extent post-exposure treatment of abrin poisoning.

Keywords

• intracellular delivery
• neutralizing antibody
• abrin
• sesbania mosaic virus
• silica nanoparticle