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Research Article

Temperature-regulated self-assembly of lipids at free bubbles interface: A green and simple method to prepare micro/nano bubbles

Juan Jin1, Fang Yang1( ), Bin Li1, Dong Liu2,3, Lihong Wu4, Yan Li1, Ning Gu1( )
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China
West Anhui University, Lu’an 237012, China
Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Lu’an 237012, China
CSPC Zhongqi Pharmaceutical Technology (SJZ) Co., Ltd., Shijiazhuang 050035, China
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Graphical Abstract

Abstract

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 (Tm), 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 Tm 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 μm, 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.

Keywords

lipidself-assemblygas-liquid interfacemicrobubblesnanobubblesultrasound imaging

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Nano Research
Volume 13 Issue 4,
April 2020
Pages 999-1007
DOI: 10.1007/s12274-020-2732-x
Cite this article:
Jin J, Yang F, Li B, et al. Temperature-regulated self-assembly of lipids at free bubbles interface: A green and simple method to prepare micro/nano bubbles. Nano Research, 2020, 13(4): 999-1007. https://doi.org/10.1007/s12274-020-2732-x
Topics:
LipidsMedical applicationsMicelles Self assemblyTheranosticsUltrasonic imaging

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Received: 10 January 2020
Revised: 24 February 2020
Accepted: 25 February 2020
Published: 11 April 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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