An archaeal protein nanoparticle platform for cancer cell-specific targeting and therapeutics

With the occurrence of new cancers and emerging diseases, there is an urgent need for development of rapidly customizable high-density display virus-like particle platforms for vaccine, cell-targeting, and drug-delivery. Gas vesicle nanoparticles (GVNPs) have been explored for their potential application as a novel type of macromolecular platform for displaying target proteins on their surface. Here we present the biomolecular engineering of a two-component GVNP platform that exploits its facile production, biocompatibility, and delivery system. We have demonstrated the production of a hybrid GVNP production system of a designer platform with concurrent binding of multiple antibodies at high density on the nanoparticle surface, for use in designer cancer therapeutics. The multivalent antibody displaying capability of the hybrid GVNP system was proven through saturation binding analysis of the recombinant GvpC fused with antibody binding sites and by simultaneous detection of two kinds of secondary antibodies labeled with different fluorescence tags on a surface of individual GVNPs. Flow cytometric analysis confirmed that GVNPs bioengineered to display cancer cell-specific NPB-40 antibodies bind to hepatoma-derived Huh-7 cells, proving their successful application as molecular carriers capable of antibody-guided targeting. Subsequently, construction of GVNPs displaying both cell-specific antibodies and antibody drug conjugates resulted in a drastic decrease in Huh-7 cell viability. These findings demonstrate that the bioengineered GVNP system can be successfully used as a multiple-antibody display platform technology that can be applied as a cancer cell-targeting molecular carrier and therapeutic system.