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 (O-1(2)) 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 O-2), but also exhibit outstanding capability for O-1(2) production, at approximate to 2.15 and 1.70 times augmented O-1(2), respectively. Both in vitro and in vivo studies demonstrate the synergetic O-1(2)-mediated inhibition of tumor proliferation, lending this strategy great potential for the treatment of hypoxic tumors.

Automated summary

This study presents an efficient multi-pathway singlet oxygen (O-1(2)) generation system for superactive biocatalytic tumor therapy, utilizing compartmental hierarchical nanoreactors. The system achieves increased efficacy by enhancing direct substrate diffusion and reducing external diffusion, showing outstanding capability for O-1(2) production. Both in vitro and in vivo studies demonstrate the synergetic O-1(2)-mediated inhibition of tumor proliferation, showcasing great potential for the treatment of hypoxic tumors.