Modulation of Carbon Nanotubes' Perturbation to the Metabolic Activity of CYP3A4 in the Liver

The liver plays an important role in metabolizing foreign materials, such as drugs. The high accumulation of carbon nanotubes and other hydrophobic nanoparticles in the liver has raised concerns that nanoparticles may interfere with liver metabolic function. We report here that carbon nanotubes enter hepatic cells after intravenous introduction and interact with CYP enzymes, including CYP3A4. Surface chemical modifications alter the carbon nanotubes' interactions with CYP450 enzymes in human liver microsomes. They enhance, inhibit, or have no effect on the enzymatic function of CYP3A4. Using a cheminformatics analysis, certain chemical structures are identified on the surface of the carbon nanotubes that induce an enzyme inhibitory effect or prevent disruption of CYP3A4 enzymes.