Site‐Specific Antibody Assembly on Nanoparticles via a Versatile Coating Method for Improved Cell Targeting

Abstract Antibody‐nanoparticle conjugates are promising candidates for precision medicine. However, developing a controllable method for conjugating antibodies to nanoparticles without compromising the antibody activity represents a critical challenge. Here, a facile and generalizable film‐coating method is presented using zeolitic imidazole framework‐8 (ZIF‐8) to immobilize antibodies on various nanoparticles in a favorable orientation for enhanced cell targeting. Different model and therapeutic antibodies (e.g., Herceptin) are assembled on nanoparticles via a biomineralized film‐coating method and exhibited high antibody loading and targeting efficiencies. Importantly, the antibodies selectively bind to ZIF‐8 via their Fc regions, which favorably exposes the functional Fab regions to the biological target, thus improving the cell targeting ability of antibody‐coated nanoparticles. In combination, molecular dynamics simulations and experimental studies on antibody immobilization, orientation efficiency, and biofunctionality collectively demonstrate that this versatile site‐specific antibody conjugation method provides effective control over antibody orientation and leads to improved cell targeting for a variety of nanoparticles.