Bioactive multi-protein adsorption enables targeted mast cell nanotherapy.

Proteins readily and often irreversibly adsorb to nanomaterial surfaces, resulting in denaturation and loss of bioactivity1,2. Controlling this process to preserve protein structure and function has remained an elusive goal that would enhance the fabrication and biocompatibility of protein-based bioactive nanomaterials3-7. Here, we demonstrate that poly(propylene sulfone) (PPSU)8 nanoparticles support the controlled formation of multi-component enzyme and antibody coatings while maintaining their bioactivity. Simulations indicate that hydrophobic patches9 on protein surfaces induce site-specific dipole relaxation on PPSU surfaces to noncovalently anchor proteins without disrupting hydrogen bonding or protein structure. As proof-of-concept, a nanotherapy for enhanced antibody-based targeting of mast cells and inhibition of anaphylaxis3,4 is demonstrated in a humanized mouse model. The ratio of co-adsorbed anti-Siglec-610,11 and anti-FcεRIα antibodies is systematically optimized to effectively inhibit mast cell activation and degranulation. Protein immobilization on PPSU surfaces therefore provides a simple and rapid platform for the development of targeted nanomedicines.