Protein adsorption onto nanomaterials typically leads to denaturation and loss of biological activity. Controlling the adsorption process to maintain protein structure and function has broad application potential. Here, we report the controlled formation and maintenance of multi-component enzyme and antibody coatings supported by self-assembled poly (propylene sulfone) (PPSU) nanoparticles. Simulations have shown that hydrophobic plaques on protein surfaces induce site-specific dipole relaxation of PPSU assemblies, thereby non covalently anchoring proteins without disrupting protein hydrogen bonds or structures. As a proof of concept, a nano therapy using multiple mast cell targeted antibodies to prevent allergic reactions was demonstrated in a humanized mouse model. PPSU nanoparticles exhibit an optimized ratio of co adsorbed anti-Siglec-6 and anti Fc ε RI α antibodies, which can effectively inhibit mast cell activation and degranulation, and prevent allergic reactions. The protein immobilization on the surface of PPSU provides a simple and rapid platform for the development of targeted protein nanomedicines.