Main-chain degradable single-chain cyclized polymers as gene delivery vectors

Area of Science:

• Polymer Chemistry
• Nanotechnology
• Biomedical Engineering

Background:

• Single-chain technology (SCT) enables nanoscale polymer object fabrication but faces limitations in biological applications due to non-degradable backbones and scalability issues.
• Current SCT methods often use vinyl monomers, resulting in persistent carbon-carbon backbones unsuitable for biomedical use.
• Ultrahigh dilution conditions required for synthesis hinder large-scale production of single-chain polymer nanoparticles.

Purpose of the Study:

• To develop a versatile approach for creating backbone-degradable single-chain polymeric nanoparticles.
• To overcome the limitations of non-degradable backbones and ultrahigh dilution conditions in SCT.
• To evaluate the gene transfection capabilities and cytotoxicity of the novel degradable nanoparticles.

Main Methods:

• A one-pot RAFT copolymerization combining ring-opening addition polymerization and intramolecular cyclization was employed.
• Kinetic control and statistical manipulation of mono- and multi-vinyl monomer copolymerization facilitated in situ intramolecular cyclization.
• A cyclic allylsulfide monomer (MDTD) was used to introduce disulfide groups for backbone degradability.

Main Results:

• Backbone degradable single-chain polymeric nanoparticles were successfully synthesized under concentrated conditions.
• The nanoparticles achieved molecular weights of 10 kDa with 4.7% MDTD incorporation.
• Chemical degradation confirmed the single-chain nature and backbone degradability of the nanoparticles.
• The nanoparticles exhibited high gene transfection efficiencies and low cytotoxicities in 3T3 and HeLa cells.

Conclusions:

• A novel, scalable method for producing backbone-degradable single-chain polymeric nanoparticles was established.
• The developed nanoparticles are suitable for biomedical applications, particularly gene delivery.
• The findings pave the way for advanced nanomedicine applications utilizing degradable polymeric nanostructures.