A novel intracellular protein delivery platform based on single-protein nanocapsules

An average cell contains thousands of proteins that participate in normal cellular functions, and most diseases are somehow related to the malfunctioning of one or more of these proteins. Protein therapy(1), which delivers proteins into the cell to replace the dysfunctional protein, is considered the most direct and safe approach for treating disease. However, the effectiveness of this method has been limited by its low delivery efficiency and poor stability against proteases in the cell, which digest the protein. Here, we show a novel delivery platform based on nanocapsules consisting of a protein core and a thin permeable polymeric shell that can be engineered to either degrade or remain stable at different pHs. Non-degradable capsules show long-term stability, whereas the degradable ones break down their shells, enabling the core protein to be active once inside the cells. Multiple proteins can be delivered to cells with high efficiency while maintaining low toxicity, suggesting potential applications in imaging, therapy and cosmetics fields.