Intracellular Implantation of Enzymes in Hollow Silica Nanospheres for Protein Therapy: Cascade System of Superoxide Dismutase and Catalase

An approach for enzyme therapeutics is elaborated with cell‐implanted nanoreactors that are based on multiple enzymes encapsulated in hollow silica nanospheres (HSNs). The synthesis of HSNs is carried out by silica sol–gel templating of water‐in‐oil microemulsions so that polyethyleneimine (PEI) modified enzymes in aqueous phase are encapsulated inside the HSNs. PEI‐grafted superoxide dismutase (PEI‐SOD) and catalase (PEI‐CAT) encapsulated in HSNs are prepared with quantitative control of the enzyme loadings. Excellent activities of superoxide dismutation by PEI‐SOD@HSN are found and transformation of H2O2 to water by PEI‐CAT@HSN. When PEI‐SOD and PEI‐CAT are co‐encapsulated, cascade transformation of superoxide through hydrogen peroxide to water was facile. Substantial fractions of HSNs exhibit endosome escape to cytosol after their delivery to cells. The production of downstream reactive oxygen species (ROS) and COX‐2/p‐p38 expression show that co‐encapsulated SOD/CAT inside the HSNs renders the highest cell protection against the toxicant N,N′‐dimethyl‐4,4′‐bipyridinium dichloride (paraquat). The rapid cell uptake and strong detoxification effect on superoxide radicals by the SOD/CAT‐encapsulated hollow mesoporous silica nanoparticles demonstrate the general concept of implanting catalytic nanoreactors in biological cells with designed functions. Superoxide dismutase and catalase encapsulated in hollow silica nanospheres as a nanoreactor results in cascade reactions converting superoxide ions into water and oxygen. Upon uptake in Hela cells, the nanoreactor protects the cell against reactive oxygen species.