Construction of robust protein nanocage by designed disulfide bonds for active cargo molecules protection in the gastric environment.

Notwithstanding the progress made, cargo molecules encapsulated within ferritin via oral administration in the gastric environment remains a persistent challenge. This study focuses on the strategic enhancement of ferritin stability in harsh gastric environment. By taking advantagie of computational-assisted design, we strategically introduced up to 96 disulfide bonds along three key inter-subunit interfaces to one single ferritin molecule with human H-chain ferritin and shrimp (Marsupenaeus japonicus) ferritin as starting materials, producing two kinds of robust ferritin nanocages with markedly enhanced acid and protease (pepsin and rennin) resistance.