Visualizing semipermeability of the cell membrane using a pH-responsive ratiometric AIEgen

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Drug Delivery

Background:

• Chemotherapy faces challenges with basic drugs ionizating in acidic tumor microenvironments, hindering cell membrane penetration.
• This ionization phenomenon, known as ion trapping, limits drug efficacy and requires novel visualization strategies.

Purpose of the Study:

• To develop and validate a novel method for visualizing the ion trapping phenomenon in real-time.
• To assess the utility of a pH-responsive, aggregation-induced emission (AIE) fluorescent probe, dihydro berberine (dhBBR), for this purpose.

Main Methods:

• Utilized a pH-responsive ratiometric AIEgen, dihydro berberine (dhBBR), as a bioprobe.
• Observed intracellular fluorescence of dhBBR under varying pH conditions mimicking tumor microenvironments.
• Compared the anti-photobleaching capabilities of dhBBR with Curcumin.

Main Results:

• Demonstrated that non-ionized dhBBR permeates cell membranes more effectively than its ionized form, confirming the ion trapping concept.
• dhBBR exhibited superior anti-photobleaching properties compared to Curcumin, attributed to its AIE characteristics.
• Successfully visualized the intracellular distribution and behavior of dhBBR in response to pH changes.

Conclusions:

• Dihydro berberine (dhBBR) effectively visualizes the ion trapping phenomenon in cancer chemotherapy.
• dhBBR's pH-responsiveness and AIE properties make it a promising bioprobe for studying drug-cell interactions.
• This approach offers potential for optimizing drug delivery strategies in acidic tumor microenvironments.