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A Compartmental Silica Nanoreactor for Multienzyme‐Regulated Superactive Catalytic Therapy

Many tumor therapies take advantage of upsetting the redox balance in tumor cells, but to do so requires excessive biochemical or physical attacks. The high‐throughput simulation using multi‐pathway techniques described herein can yield an increased efficacy in bio‐oxidation. In this study, compartmental hierarchical nanoreactors are developed as an efficient multi‐pathway singlet oxygen (1O2) generation system for superactive biocatalytic tumor therapy. The penetrated super cavity and connected dual‐mesopore channels of the compartmental multienzyme nanoreactors are designed using the proposed heterogeneous template assembly for multi‐enzyme complex (superoxide dismutase (SOD)‐lactoperoxidase (LPO)) and photosensitizer molecule (indocyanine green (ICG)) encapsulation. Benefiting by the enhanced direct substrate diffusion between the interacting SOD–LPO complex and decrease in external diffusion, the parallel catalysis combined by the superactive cascade biocatalysis and enzyme‐promoted photosensitization effect is verified by this compartmental silica nanoreactor system. The parallel pathways not only make full use of the products of SOD (H2O2 and O2), but also exhibit outstanding capability for 1O2 production, at ≈2.15 and 1.70 times augmented 1O2, respectively. Both in vitro and in vivo studies demonstrate the synergetic 1O2‐mediated inhibition of tumor proliferation, lending this strategy great potential for the treatment of hypoxic tumors.