Folate-conjugated thermoresponsive block copolymers: highly efficient conjugation and solution self-assembly

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Developing targeted drug delivery systems is crucial for enhancing cancer therapy efficacy.
• Stimuli-responsive polymers offer controlled drug release mechanisms.
• Click chemistry provides efficient conjugation of biomolecules to polymers.

Purpose of the Study:

• To synthesize temperature-responsive block copolymer micelles conjugated with folic acid for active targeting of cancer tissues.
• To investigate the self-assembly behavior and drug release capabilities of these nanostructures.
• To evaluate the potential of azide-alkyne click chemistry for creating functionalized polymer assemblies.

Main Methods:

• Synthesis of N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMA) block copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization using an azido chain transfer agent (CTA).
• Conjugation of folic acid using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with propargyl folate.
• Characterization of polymerizations and self-assembly into micelles.
• Assessment of drug release from the micelles.

Main Results:

• RAFT polymerization yielded polymers with controlled molecular weights and narrow polydispersity.
• Efficient conjugation of folic acid to the polymer chain ends was achieved via CuAAC.
• Temperature-induced self-assembly formed micelles capable of encapsulating and releasing a model hydrophobic drug.
• The developed method demonstrates a versatile platform for creating targeted, stimuli-responsive nanocarriers.

Conclusions:

• The combination of RAFT polymerization and click chemistry enables the preparation of folate-conjugated, temperature-responsive block copolymer micelles.
• These micelles show potential for active targeting of cancer cells and controlled drug delivery.
• The strategy is adaptable for incorporating other stimuli-responsive elements and targeting ligands for diverse biomedical applications.