A reactive oxygen species-triggerable theranostic prodrug system

Area of Science:

• Biomedical Engineering
• Organic Chemistry
• Oncology

Background:

• Elevated reactive oxygen species (ROS) are a hallmark of tumors, driving interest in ROS-activated prodrugs.
• Existing ROS-activated molecular triggers lack sensitivity and ease of functionalization for specific prodrug development.

Purpose of the Study:

• To develop a highly reactive oxygen species (hROS)-responsive molecular trigger with integrated imaging and therapeutic capabilities.
• To synthesize and evaluate novel prodrugs utilizing this trigger for targeted cancer therapy.

Main Methods:

• Conjunction of methylene blue (MB) and 2,6-bis(hydroxymethyl)aniline via a urea bond to create the FDROS-4 trigger.
• Modification of FDROS-4 with chlorambucil and galactose ligands to create liver-targeting prodrugs (FDROS-6, -7, -8).
• Assessment of prodrug self-assembly, biocompatibility, and therapeutic efficacy.

Main Results:

• The developed FDROS-4 trigger is efficiently activated by hROS (•OH, ONOO-, HOCl), releasing MB and parent drugs.
• Liver-targeting prodrugs were successfully synthesized, with FDROS-7 showing optimal performance.
• FDROS-7 self-assembled into nanoparticles, demonstrating improved biocompatibility and therapeutic efficacy over the parent drug.

Conclusions:

• The novel hROS-activated molecular trigger (FDROS-4) offers high sensitivity and functionalization potential.
• Targeted prodrugs, like FDROS-7, show promise for enhanced chemotherapy delivery and efficacy.
• This platform holds potential for developing advanced stimulus-responsive prodrugs.