Development of fluorous lipid-based nanobubbles for efficiently containing perfluoropropane

Area of Science:

• Nanotechnology
• Biomaterials Science
• Medical Imaging

Background:

• Nano- and microbubbles are utilized as ultrasound contrast agents and for ultrasound-triggered gene/drug delivery.
• Nanobubbles offer passive tumor targeting via tumor vasculature penetration, making them promising for ultrasound-mediated cancer theranostics.
• Challenges exist in nanobubble gas content, which is lower than microbubbles due to smaller volumes, impacting injection volume and echogenicity.

Purpose of the Study:

• To develop nanobubbles with higher gas content and improved echogenicity.
• To investigate the use of fluoro-lipids as stabilizers for encapsulating nanobubbles within liposomes.
• To enhance the efficiency of nanobubbles as fluorous gas carriers for theranostic applications.

Main Methods:

• Preparation of five types of fluoro-lipids to act as surfactants for stabilizing nanobubbles within liposomes, termed "Bubble liposomes".
• Encapsulation of nanobubbles within liposomes, with lipids stabilizing the interface between fluorous gas and aqueous phases.
• Characterization of Bubble liposomes containing a specific fluoro-lipid (1-stearoyl-2-(18,18-difluoro)stearoyl-sn-glycero-3-phosphocholine) for gas content and echogenicity.

Main Results:

• Bubble liposomes incorporating fluoro-lipids demonstrated significantly enhanced stabilization of nanobubbles.
• The modified Bubble liposome containing 1-stearoyl-2-(18,18-difluoro)stearoyl-sn-glycero-3-phosphocholine carried double the amount of C3F8 gas compared to unmodified Bubble liposomes.
• Ultrasonography confirmed increased echogenicity of the modified Bubble liposomes.

Conclusions:

• The incorporation of fluoro-lipids is a highly effective strategy for creating nanobubbles with increased fluorous gas carrying capacity.
• This approach offers a promising method for developing advanced nanobubbles with enhanced echogenicity for improved ultrasound imaging and theranostic applications.
• The developed Bubble liposomes represent a significant advancement in nanobubble technology for cancer theranostics.