Effective Control of Enzyme Activity Based on a Subtle Nanoreactor: A Promising Strategy for Biomedical Applications in the Future

Therapeutic enzymes have been considered as a promising candidate for various medical applications due to their high specificity. However, how to maintain the enzymatic stability in the long-term, while performing the tunable activity of a certain enzyme for different physiological requirements, is still a challenge. Herein, a time and ratio associated method was employed to form a silica shell with controllable nanopores on the surface of the enzyme as a nanoreactor for preserving and freely tailoring its activity. The model enzymes (α-amylase and glucose oxidase) entrapped in these silica nanoreactors are able to perform a distinct activity as designed with up to a 10-fold difference, while the lifecycle and tolerability to harsh conditions (pH and temperature) are all dramatically enhanced compared with those of free enzymes. Moreover, this modified enzyme was used for tumor therapy and presented excellent performance. The silica-covered glucose oxidase (GO) associating with l-arginine (Arg) modification could be easily delivered to tumor cells and then exhibited high persistence of the activity in cytoplasm, which is able to convert glucose to H₂O₂ (GO) and finally generate NO (Arg) in tumor cells, resulting in high cell cytotoxicity for tumor therapy. The high efficacy of our device in tumor therapy indicates that this approach could be broadly used to engineer enzymes for different biological applications.