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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Novel Cells-Based Electrochemical Sensor for Investigating the Interactions of Cancer Cells with Molecules and
Cong Li1, Yinzhu Cui1, Jinyu Ren1
1Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
Abstract:
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.
Insights
A novel electrochemical sensor detects molecular interactions with cancer cells. This method, using N-doped graphene-Pt nanoparticles-chitosan and polyaniline, screens compounds and analyzes drug targets without monitoring cell behavior changes.
Area of Science:
- Electrochemistry
- Biomolecular Interactions
- Nanomaterials Science
Background:
- Developing label-free electrochemical sensors is crucial for understanding molecular interactions with cancer cells.
- Existing cell-based sensors often rely on monitoring drug-induced cell behavior changes, limiting their scope.
- Novel methods are needed to directly assess molecular binding to specific cancer cell types.
Purpose of the Study:
- To construct a novel, label-free electrochemical sensor for investigating cancer cell-molecule interactions.
- To screen compounds from Aidi injection (ADI) for interactions with HepG2 and A549 cancer cells.
- To analyze potential molecular targets using computer-aided methods.
Main Methods:
- Fabrication of a bilayer sensor using N-doped graphene-Pt nanoparticles-chitosan (NGR-Pt-CS) and polyaniline (PANI).
- Immobilization of targeted cancer cells (HepG2, A549) on the modified electrode surface.
- Measurement of current changes in [Fe(CN)6]3-/4- to quantify interactions and calculation of binding constants via sensing kinetics.
- Screening of 18 components from Aidi injection (ADI) and molecular docking analysis.
Main Results:
- The sensor successfully detected interactions between cancer cells and molecules like folic acid (FA).
- Binding constants were calculated as 1.37 × 105 M-1 for HepG2 and 1.92 × 105 M-1 for A549 cells.
- Screening identified compounds from ADI that interact with HepG2 and A549 cells, with potential targets analyzed via molecular docking.
Conclusions:
- The developed sensor provides a simple, effective, and generally applicable platform for exploring molecule-cancer cell interactions.
- This method circumvents the limitations of traditional cell-based sensors by directly measuring binding events.
- The sensor is valuable for screening multitarget drugs and understanding drug-target interactions in cancer research.
