Nanobiohybrid Extracellular\nVesicle Nanoreactor with\nImproving Metabolical Activity for Biocatalytic Therapy

Extracellular vesicles (EVs) hosting enzymatic activities\nthat\nfunction as independent metabolic units are attractive natural biocatalytic\nplatforms. However, directly using these metabolically active nanoreactors\nfor effective biocatalytic applications remains challenging, mainly\ndue to their constrained catalytic capabilities. Here, we construct\nan EV-templated nanobiohybrid system by engineering an EV surface\nwith a photoresponsive zeolitic imidazolate framework (ZIF). The deposition\nof ZIF nanostructures on EVs not only contributes to improved biocatalytic\nstability but also enables interfacial coupling between photoexcited\nelectrons from the ZIF and the enzymatic reaction of metabolically\nactive EVs. Nearly 300% of biomass conversion efficiency increment\ncould be achieved by EVs derived from macrophages. This enhanced biocatalysis,\nhigh catalytic stability, and low cytotoxicity endowed the EV@ZIF\nnanosystem with robust biosynthesis and antimicrobial activity. When\nevaluated in a mouse periodontitis model, we show that the autologous\nbiocatalytic EV@ZIF demonstrated efficient therapeutic capability\nby killing bacteria and inhibiting inflammation. This nanoengineering\nstrategy will benefit the future optimization of metabolically active\nEV nanoreactors as biocatalysts for a broad range of therapeutics.