Supramolecular Nanofibers of Drug‐Peptide Amphiphile and Affibody Suppress HER2+ Tumor Growth

Abstract Antibody‐based medicines and nanomedicines are very promising for cancer therapy due to the high specificity and efficacy of antibodies. However, antibody‐drug conjugates and antibody‐modified nanomaterials frequently suffer from low drug loading and loss of functions due to the covalent modification of the antibody. A novel and versatile strategy to prepare supramolecular nanomaterials by the coassembly of an affibody (antiHER2) and drug‐peptide amphiphiles is reported here. During the enzyme‐instructed self‐assembly process, the drug‐peptide amphiphile can coassemble with the affibody, resulting in supramolecular nanofibers in hydrogels. The drug loading in the supramolecular nanofibers is high (>30 wt%), and the stability of antiHER2 is significantly improved in the nanofibers at 37 °C (>15 d in vitro). The supramolecular nanofibers exhibit high affinity for HER2+ cancer cells and can be efficiently taken up by these cells. In a mouse tumor model, the supramolecular nanofibers abolish HER2+ NCI‐N87 tumor growth due to the good accumulation and retention of nanofibers in tumor. This study provides a novel strategy to prepare nanomedicines with high drug loading and high specificity.