Synthesis and Self-Assembly of Degradable Peptide-Grafted PEG-Derivative Polymers

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Polymer-peptide conjugates offer versatile applications in drug delivery, tissue engineering, and antibacterial coatings.
• Grafting peptides onto degradable polymer backbones enhances peptide loading, controls self-assembly, and introduces degradability.

Purpose of the Study:

• To synthesize novel degradable polyethylene glycol (PEG)-derivative polymers functionalized with octa-arginine (R8) peptides.
• To investigate the self-assembly behavior and drug delivery capabilities of these peptide-grafted polymers.

Main Methods:

• Synthesis of P(PEG) polymers via Passerini polymerization, incorporating disulfide linkages and adamantyl groups.
• Functionalization with β-cyclodextrin (β-CD)-modified R8 peptide and mPEG using molecular recognition.
• Characterization of self-assembly into nanoparticles and polymersomes, and assessment of degradation in glutathione solution.
• Evaluation of nanocarrier performance for doxorubicin delivery into 4T1 cells.

Main Results:

• Peptide-grafted PEG-derivative polymers self-assembled into various structures, including nanoparticles and polymersomes (160 nm to over 1 μm), with tunable properties based on polymer architecture.
• Disulfide bonds in the polymer backbone enabled efficient degradation into <10 nm fragments in glutathione.
• The assemblies demonstrated effective loading and delivery of doxorubicin (DOX) into 4T1 cancer cells.
• DOX-loaded nanocarriers induced apoptosis in cancer cells.

Conclusions:

• Degradable peptide-grafted PEG-derivative polymers can be precisely engineered for controlled self-assembly and drug delivery.
• These nanocarriers show promise for targeted cancer therapy, leveraging their size-tunable assembly, degradability, and cellular uptake.
• The developed materials represent a significant advancement in the field of polymer-peptide conjugates for biomedical applications.