Nanobiohybrid Extracellular Vesicle Nanoreactor with Improving Metabolical Activity for Biocatalytic Therapy

Abstract

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