Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry

Area of Science:

• Nanotechnology
• Bioconjugation Chemistry
• Drug Delivery Systems

Background:

• Nanoparticle functionalization is crucial for targeted drug delivery.
• Current methods may lack efficiency or specificity.
• Developing advanced surface modification techniques is essential.

Purpose of the Study:

• To develop a highly efficient and chemoselective method for post-functionalization of liposomes.
• To utilize a synergistic approach combining affinity and covalent anchoring tags.
• To enable versatile functionalization of nanoparticles and solid surfaces.

Main Methods:

• Synthesized a peptide linker system employing Cu-free strain-promoted click chemistry.
• Integrated histidine affinity tags with covalent anchoring for surface modification.
• Investigated post-functionalization of PEGylated liposomes using a cyclic RGDfE peptide.
• Quantified reaction kinetics and yield using High-Performance Liquid Chromatography (HPLC).

Main Results:

• Achieved a high coupling efficiency of 98 ± 2.0% using both affinity and covalent tags.
• Demonstrated significant efficiency (87 ± 0.2%) even in diluted systems.
• Validated the method's effectiveness for PEGylated liposomes and cyclic RGDfE peptide conjugation.
• HPLC analysis confirmed reaction kinetics and overall yield.

Conclusions:

• The developed method offers a powerful tool for nanoparticle and surface functionalization.
• The synergistic use of affinity and covalent tags significantly enhances coupling efficiency.
• This approach opens new avenues for constructing complex nanostructures for advanced applications.
• The method's versatility extends to various nanoparticles and solid surfaces.