Bioactive Polymeric Scaffolds: Multivalent Functionalization by Thermal Azide-Alkyne Cycloaddition with Alkynyl...

Area of Science:

• Polymer Chemistry
• Bioconjugation Chemistry
• Materials Science

Background:

• Multivalency enhances binding affinity and specificity compared to monovalent interactions.
• Nature's strategies for biorecognition inspire the design of multivalent conjugates for therapeutic applications.
• Traditional chemical functionalization methods often involve complex procedures with coupling agents, additives, or metal catalysts, complicating purification.

Purpose of the Study:

• To present azide-alkyne cycloaddition (AAC) with alkynyl dicarbamates (Alk-R) as a versatile and user-friendly strategy for multivalent functionalization of polymeric scaffolds.
• To demonstrate the synthesis of multivalent conjugates for potential applications in drug delivery.
• To develop a platform for bioinspired functional systems with synergistic integration of probes, ligands, and drugs.

Main Methods:

• Utilized azide-alkyne cycloaddition (AAC) with alkynyl dicarbamates (Alk-R) for polymer functionalization.
• Prepared Alk-R functionalized with biologically relevant ligands.
• Applied multivalent AAC to functionalize azide-bearing dendrimers and block copolymers.

Main Results:

• Developed a flexible, reliable, atom-economical, and user-friendly strategy for multivalent functionalization.
• Created polymers with double multivalency, including block copolymer micelles and multifunctional nanocarriers.
• Demonstrated synergistic integration of probes, ligands, and drugs within nanocarriers.

Conclusions:

• The presented AAC strategy offers a simplified approach to synthesizing multivalent functionalized polymers.
• The developed multivalent systems show promise as platforms for advanced drug delivery and multifunctional nanocarriers.
• This methodology is expected to expand therapeutic and diagnostic opportunities through broader applications in ligand and scaffold design.