Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening

Area of Science:

• Biomedical Engineering
• Biochemistry
• Pharmacology

Background:

• Glucose transporter 1 (GLUT1) overexpression in tumors presents a therapeutic target.
• Current methods struggle with real-time monitoring of GLUT1 inhibitor efficacy.
• Screening natural compounds for GLUT1 inhibitors remains challenging.

Purpose of the Study:

• To develop a cell membrane-based glucose sensor (CMGS) for real-time monitoring of GLUT1 activity.
• To utilize CMGS for screening traditional Chinese medicines (TCMs) for GLUT1 inhibitors.
• To investigate glucose transport kinetics and assess drug efficacy.

Main Methods:

• Integrated a hydrogel electrode with tumor cell membranes to create CMGS.
• Tested CMGS compatibility with various tumor cell lines and GLUT1-modulated cells.
• Employed CMGS for continuous monitoring of glucose transport and inhibitor screening.
• Validated results with cellular glucose uptake assays and molecular docking.

Main Results:

• CMGS demonstrated compatibility with diverse cell membranes, including those with altered GLUT1 expression.
• Continuous monitoring revealed glucose transport kinetics related to GLUT1 levels.
• Successfully identified GLUT1-inhibitory effects of compounds from Scutellaria baicalensis and catechins.
• CMGS results aligned with traditional assays and simulations.

Conclusions:

• CMGS provides an accurate and real-time method for screening GLUT1 inhibitors from TCMs.
• This sensor offers a new strategy for studying transmembrane protein-receptor interactions.
• CMGS facilitates the discovery of novel anti-cancer therapeutics targeting GLUT1.