Cobalt-Directed Assembly of Antibodies onto Metal-Phenolic Networks for Enhanced Particle Targeting

The orientation-specific immobilization of antibodies onto nanoparticles, to preserve antibody-antigen recognition, is a key challenge in developing targeted nanomedicines. Herein, we report the targeting ability of metal-phenolic network (MPN)-coated gold nanoparticles with surface-physisorbed antibodies against respective antigens. The MPN coatings were self-assembled from metal ions (Fe^III, Co^II, Cu^II, Ni^II, or Zn^II) cross-linked with tannic acid. Upon physisorption of antibodies, all particle systems exhibited enhanced association with target antigens, with Co^II systems demonstrating more than 2-fold greater association. These systems contained more metal atoms distributed in a way to specifically interact with antibodies, which were investigated by molecular dynamics simulations. A model antibody fragment crystallizable (Fc) region in solution with Co^II-tannic acid complexes revealed that the solvent-exposed Co^II can directly coordinate to the histidine-rich portion of the Fc region. This one-pot interaction suggests anchoring of the antibody Fc region to the MPN on nanoparticles, allowing for enhanced targeting.