Photochemical Bionanoreactor for Efficient Visible-Light-Driven in Vitro Drug Metabolism.

Abstract

In light of the significance of cytochrome P450 (CYP) catalyzed drug metabolism for drug development and toxicity screening, it is very important to imitate natural metabolic pathways accurately and efficiently in vitro. Herein, a novel and simple photochemical bionanoreactor has been constructed for efficient visible-light-driven in vitro drug metabolism based on eosin-Y-functionalized macroporous ordered silica foams (MOSF-EY). Because of the unique transfer of photoinduced electrons from photosensitizers to CYP heme domain, CYP catalyzed drug metabolism can be in vitro driven by the MOSF-EY nanoreactor under the irradiation of visible light. In such a case, the utilization of expensive electron donors, such as NADPH, can be avoided. Meanwhile, the in vitro drug metabolism approach exhibits high efficiency because of the fast adsorption of both CYP and drug molecules from the bulk solution into the nanopores of MOSF-EY, where the enzyme and substrate are highly concentrated and confined in nanospace to achieve a high reaction rate. Taking advantage of these attractive merits, the first example of photochemical bionanoreactor has been successfully applied in in vitro metabolism of both purified drug molecules and real tablets. Not only excellent CYP-catalyzed drug metabolism but also enzyme inhibition assay has been performed with the MOSF-EY photochemical bionanoreactor.