Nanohybrids of quantum dots and cytochrome P450 for light-driven drug metabolism

• The photocatalyst composing of CYP2D6 and CdTe QDs is prepared by carbodiimide coupling chemistry.
• The photocatalyst exhibit excellent photocatalytic activity towards tramadol metabolism.
• The PEC platform in-situ monitor the light-driven drug metabolism and enzyme inhibition.
• The Kmapp was easily obtained with the proposed PEC system.
• A mechanism for light-driven drug metabolism was proposed.

In this work, nanohybrids of CdTe quantum dots (QDs) and cytochrome P450 2D6 (CYP2D6) prepared by covalent binding of CYP2D6 to QDs were used as photocatalysts for drug metabolism. As a proof-of-concept of the light-driven drug metabolism, tramadol was chosen as the substrate. As control, the high performance liquid chromatography coupled with mass spectrometry (HPLC–MS) was used to confirm the production of metabolites. Under irradiation with a white-light, the catalytic cycle of P450-mediated oxygenation reactions occurred with the formation of radical species on QDs, which immediately activated the proximity of the bound P450 enzyme and transferred electrons from the conduction band (CB) of CdTe QDs to CYP2D6. This light-driven catalytic reaction via nanohybrids was comparable to the native biological metabolism by CYP2D6 isozyme microsomes with CYP reductase (CPR) using the enzyme cofactor nicotinamide-adenine dinucleotide phosphate (NADPH) as electron donor. Furthermore, a photoelectrochemical platform was designed for in-situ monitoring the metabolic reactions. Upon addition of tramadol, the photocurrent increased due to the electron transfer from the CB of CdTe QDs to CYP2D6. The apparent Michaelis–Menten constant was thus easily measured to be 1.35 μM. This enzyme-based photoelectrochemical platform showed accepted stability and great potential for studies on drug metabolism in vitro.

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