Flucytosine-based prodrug activation by cold physical plasma

Area of Science:

• Chemistry
• Biomedical Engineering
• Materials Science

Background:

• Reactive oxygen species (ROS) are crucial for activating arylboronate-containing prodrugs, particularly in cancer therapy.
• Elevated ROS levels in cancer cells enable selective prodrug activation through Baeyer-Villiger oxidation.
• Cold physical plasma (CPP) offers a novel approach to trigger these oxidation-rearrangement cascades.

Purpose of the Study:

• To investigate CPP as a trigger for ROS-responsive prodrug activation.
• To synthesize and test a 5-fluorocytosine (5-FC) based prodrug analog for CPP responsiveness.
• To establish a proof of concept for CPP-initiated prodrug activation cascades.

Main Methods:

• Synthesis of a 5-fluorocytosine (5-FC) prodrug analog.
• Exposure of the prodrug to cold physical plasma (CPP).
• Analysis of the prodrug's chemical transformation and drug release.

Main Results:

• CPP successfully initiated the envisioned oxidation and rearrangement cascade.
• The successive loss of boronic acid species was observed.
• Spontaneous liberation of the model drug 5-FC was inefficient in this specific case.

Conclusions:

• Cold physical plasma (CPP) can initiate prodrug activation cascades, offering an alternative to ROS.
• The model prodrug demonstrated CPP-induced chemical transformation but limited drug release.
• Custom-tailored CPP-responsive prodrugs represent a promising, evolving research direction.