Smart BioorthogonalCatalytic Factory for GlaucomaTherapy

Glaucoma is characterized by high intraocular pressure (IOP), oxidative stress, and distinct optic nerve damage. Natural enzymes have unparalleled advantages in the treatment of glaucoma due to their high efficiency, specificity, and selectivity. However, their poor stability and recoverability have constrained their application. The selection of good immobilization carriers is an effective strategy to protect natural enzymes. Here, we employ a mild room-temperature aqueous-phase enzyme immobilization technique to immobilize superoxide dismutase and catalase. Then, l-arginine is added to the pores and further modified with DSPE-mPEG to construct a bioorthogonal catalytic factory (SC@COF-L-D) with excellent biocompatibility. This strategy greatly protects the natural enzyme from inactivation and improves the operational stability. SC@COF-L-D can scavenge a large amount of reactive oxygen species to reduce oxidative/nitrative damage and activate the soluble guanylate cyclase pathway, thereby lowering the IOP for effective treatment of glaucoma. This work provides a paradigm for the design of materials for glaucoma therapy.