Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

Area of Science:

• Polymer Chemistry
• Materials Science
• Nanotechnology

Background:

• Cyclic and linear polymers exhibit distinct physical properties.
• Exploiting these differences for clinical applications remains underexplored.
• Graft copolymer assemblies offer potential for drug delivery systems.

Purpose of the Study:

• To investigate the stability of cyclic-linear graft copolymer assemblies compared to linear-linear counterparts.
• To demonstrate triggered disassembly of these assemblies for controlled drug release.
• To explore the potential of polymer topology as a trigger for drug delivery vehicles.

Main Methods:

• Synthesis of cyclic-linear and linear-linear graft copolymers.
• Formation and characterization of self-assembled nanoparticles.
• Triggered disassembly using disulfide reduction in the presence of l-glutathione.
• In vitro evaluation of anti-cancer drug release.

Main Results:

• Cyclic-linear graft copolymer assemblies showed significantly higher stability than linear-linear assemblies.
• Disassembly was successfully triggered by cleaving a single bond in the cyclic polymer backbone.
• Demonstrated topology-controlled particle disassembly for controlled release of an anti-cancer drug.
• Achieved controlled release of an anti-cancer drug in vitro.

Conclusions:

• Polymer topology significantly impacts self-assembly stability and disassembly behavior.
• A change in polymer topology can serve as a trigger for controlled release from nanoparticles.
• This approach offers a novel strategy for targeted delivery of therapeutic agents.
• Cyclic-linear graft copolymers hold promise for advanced drug delivery applications.