Enhanced Metabolic Activity of Cytochrome P450 via Carbon Nanocage-Based Photochemical Bionanoreactor

Recently, the early screening of the genotoxicity of new chemicals and drugs calls for the envelope of micro-/nanoreactors for metabolic study. Herein, a novel light-driven enzymatic bionanoreactor is designed with the gold nanoparticle (NP)-modified carbon nanocage (Au@CNC) as a nanoreactor and meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) as a photosensitizer for cytochrome P450-mediated drug metabolism. By confining the cytochrome P450 3A4 (CYP3A4) enzyme and TCPP inside the pores of Au@CNC, a high metabolic activity is achieved by using 7-ethoxytrifluoromethyl coumarin as the substrate because of the three-dimensional hierarchical porous structure, large surface area, and fast electron transfer capacity of Au@CNC. It is noted that owing to the presence of AuNPs inside CNC, the surface hydrophilicity of CNC is much improved, which further promotes the catalytic activity of the CYP3A4 enzyme. To our knowledge, this is the first attempt to apply CNC as a bionanoreactor for NADPH-free and light-driven in vitro drug metabolism. In addition, the presented bionanoreactor exhibits a variety of advantages in terms of fast response, short assay time (10 min), high sensitivity, and good selectivity, which are expected to expedite drug screening and render potential advances in drug discovery and development.