Novel Cells-Based Electrochemical Sensor for Investigating the Interactions of Cancer Cells with Molecules and Screening Multitarget Anticancer Drugs.

A novel, effective, and label-free electrochemical sensor was constructed for investigating the interactions between cancer cells and molecules, based on targeted cancer cells immobilized on a bilayer architecture of N-doped graphene-Pt nanoparticles-chitosan (NGR-Pt-CS) and polyaniline (PANI). The interactions between folic acid (FA, positive control) and dimethyl sulfoxide (DMSO, negative control) and the choice of targeted cells, HepG2 and A549 cells, were investigated by measuring the current change of the sensor to [Fe(CN)6]3-/4- before and after interactions, and the binding constants were calculated to be 1.37 × 105 and 1.92 × 105 M-1 by sensing kinetics. Furthermore, 18 main components from Aidi injection (ADI) were studied to screen compounds that have interactions with different targeted cancer cells including HepG2 and A549 cells. The potential target groups of the interactions between screened active compounds and targeted cancer cells were analyzed through computer-aided molecular docking. In this sensing system, molecules did not require electrochemical activity, and different targeted cancer cells could be immobilized on the modified electrode surface, truly reflecting the categories and numbers of targets. Additionally, the proposed sensor specifically circumvented the current paradigm in most cells-based electrochemical sensors for screening drugs, in which the changes in cell behavior induced by drugs are monitored. This study provided a novel, simple, and generally applicable method for exploring the interaction of molecules with cancer cells and screening multitarget drugs.