A Novel Approach to Making the Gas-Filled Liposome Real: Based on the Interaction of Lipid with Free Nanobubble within the Solution

Nanobubbles with a size less than 1 μm could make a promising application in ultrasound molecular imaging and drug delivery. However, the fabrication of stable gas encapsulation nanobubbles is still challenging. In this study, a novel method for preparation of lipid- encapsulated nanobubbles was reported. The dispersed phospholipid molecules in the prefabricated free nanobubbles solution can be assembled to form controllable stable lipid encapsulation gas-filled ultrasound-sensitive liposome (GU-Liposome). The optimized preparation parameters and formation mechanism of GU-Liposome were investigated in detail. Results showed that this type of GU-Liposome had mean diameter of 194.4 ± 6.6 nm and zeta potential of -25.2 ± 1.9 mV with layer by layer self-assembled lipid structure. The acoustic imaging analysis in vitro indicated that ultrasound imaging enhancement could be acquired by both perfusion imaging and accumulation imaging. The imaging enhancement level and duration time was related with the ratios of lipid to gas in the GU-Liposome structure. All in all, by this novel and controllable nanobubble construction technique, it will broaden the future theranostic applications of nanobubbles.