Click modification of multifunctional liposomes bearing hyperbranched polyether chains

Area of Science:

• Biotechnology
• Materials Science
• Nanotechnology

Background:

• Liposomes are versatile drug delivery vehicles, but controlling their surface properties for specific applications remains challenging.
• Steric stabilization is crucial for liposome stability and circulation time.
• Post-preparational surface modification offers flexibility in tailoring liposome functionality.

Purpose of the Study:

• To develop a post-preparational method for surface derivatization of multifunctional, sterically stabilized liposomes.
• To utilize dual centrifugation (DC) for efficient liposome formulation and surface modification optimization.
• To explore the use of clickable hyperbranched amphiphiles for surface conjugation via click chemistry.

Main Methods:

• Formulation of sterically stabilized liposomes using cholesterol-polymer amphiphiles with terminal alkyne groups via dual centrifugation (DC).
• Surface conjugation of small molecules (e.g., fluorophores) to liposomes using click chemistry.
• Monitoring of conjugation reactions and liposome-cell interactions using Förster resonance energy transfer (FRET) spectroscopy.

Main Results:

• High encapsulation efficiencies (>50%) achieved with small batch sizes (150 μL) using DC.
• Successful conjugation of 350-450 fluorophores per liposome via click chemistry, demonstrating surface modification capability.
• Monitoring of FRET-labeled liposome uptake by RBE4 cells and analysis of lipid distribution within cellular structures.

Conclusions:

• The combination of clickable hyperbranched amphiphiles and dual centrifugation enables the creation of well-defined liposomal formulations with diverse surface moieties.
• This approach facilitates controlled liposome surface modification for advanced applications, including targeted delivery and cellular studies.
• The method offers a versatile platform for developing next-generation liposomal therapeutics and research tools.