Sheltering proteins from protease-mediated degradation and a de novo strategy for preventing acute liver injury

Restoring protein functions or supplying proteins is considered one of the most powerful therapeutic strategies for many diseases, but it is mainly limited by the denaturation of proteins during encapsulation and degradation by proteases during in vivo delivery, and limits its delivery. Herein, by encapsulating a protein (catalase, an enzyme) in a hexahistidine-metal assembly (HmA) via a de novo strategy under mild conditions, we demonstrated that HmA could maintain the bioactivity of the enzyme, protect the enzyme from proteinase degradation, and deliver the encapsulated protein for the prevention of disease in an acute liver injury model.