Journal
NANO RESEARCH
Volume 13, Issue 4, Pages 999-1007Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-020-2732-x
Keywords
lipid; self-assembly; gas-liquid interface; microbubbles; nanobubbles; ultrasound imaging
Categories
Funding
- National Key Research and Development Program of China [2017YFA0104302, 2018YFA0704103]
- National Natural Science Foundation of China [61821002, 51832001]
- Natural Science Foundation of Jiangsu Province [BK20191266]
- Zhong Ying Young Scholar of Southeast University
- Fundamental Research Funds for the Central Universities
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Micro/nanobubbles play an essential role in ultrasound-based biomedical applications. Here, a green and simple method to fabricate micro/nanobubbles was developed by the temperature-regulated self-assembly of lipids in the presence of free bubbles. The self-assembly mechanism of lipids interacting with gas-water interfaces was investigated, and the ultrasound imaging of the obtained lipid-encapsulated bubbles (LBs) was further confirmed. Above the phase transition temperature (T-m), fluid lipids transform from vesicles to micelles, and further assemble to the free bubbles interface to be a compressed monolayer, resulting in lipid shelled microbubbles. Cooling below T-m induces the lipid shell to glassy state and stables the LBs. Moreover, increasing the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2K) content in lipids formulation can further manipulate the shell curvature and reduce the LBs size into nanobubbles. LBs with diameters of 1.68 +/- 0.11 mu m, 704 +/- 7 nm and 208 +/- 6 nm were successfully prepared. The in vitro and in vivo ultrasound imaging results showed that all of the LBs had excellent echogenicity. The nanosized LBs revealed elongated imaging duration time and greater microvascular details for the liver tissue. Avoiding the organic solvent and complicated multiple preparation process, this method has great potential in construction of various multifunctional micro/nanobubbles with size control for theranostic applications.
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