Bioactive hard protein coronas on poly(propylene sulfone) surfaces enable mast cell nanotherapy

Contact between nanomaterials and biomolecules such as serum proteins leads to “soft” or “hard” corona formation via dynamic or irreversible adsorption, respectively. While soft coronas of antibodies can temporarily retain the ability for immunological recognition, preserving protein function within hard coronas has remained an elusive goal due to the unfolding of protein at the nano-bio interface. Here, we show that poly(propylene sulfone) nanoparticles efficiently and stably adsorb proteins, unexpectedly forming bioactive hard coronas using a facile methodology. This process is permitted by site-specific hydrophobic-hydrophobic interactions between nanoparticle surfaces and proteins, allowing stable simultaneous pre-adsorption of multiple proteins such as enzymes and antibodies. For therapeutic validation, a nanotherapy for enhanced antibody-based targeting of mast cells and inhibition of anaphylaxis was demonstrated in a humanized mouse model. Protein immobilization on the poly(propylene sulfone) surface therefore provides a simple and rapid platform for the design, fabrication, and optimization of bioactive and targeted nanomedicines.