Abstract
Nanobubbles (NBs) opened a new field of ultrasound imaging. There is still no practical method to control the diameter of bubbles. In this study, we developed a new method to control the size by incorporating of silicon hybrid lipids into the bubble membrane. The range of particle size of resulting NBs is between 523.02 ± 46.45 to 857.18 ± 82.90, smaller than the conventional microbubbles. The size of resulting NBs increased with the decrease in amount of silicon hybrid lipids, indicating the diameter of NBs can be regulated through modulating the ratio of silicon hybrid lipids in the bubble shell. Typical harmonic signals could be detected. The in vitro and in vivo ultrasound imaging experiments demonstrated these silicon-modified NBs had significantly improved ultrasound contrast enhancement abilities. Cytotoxicity assays revealed that these NBs had no obvious cytotoxicity to the 293 cell line at the tested bubble concentration. Our results showed that the novel NBs could use as nanoscale ultrasound contrast agents, providing the foundation for NBs in future applications including contrast-enhanced imaging and drug/gene delivery.
Highlights
Noninvasive medical imaging has played more and more important roles in clinical practice
SNB1 was prepared with formulation 1 (DSPC: DSPE-PEG2000: CFL = 45: 45: 10)
Quantitative analysis of the contrast-enhanced sonograms revealed that the mean signal intensity for the liver injected with silicon-modified nanobubble (SNB) and control MBs (Fig 7 and Table 1). All of these results demonstrated that the three SNBs exhibited acceptable in vivo performance in ultrasound imaging
Summary
Noninvasive medical imaging has played more and more important roles in clinical practice. A good example of noninvasive imaging is ultrasound imaging, which allows for repeated, non-invasive, and direct monitoring of the processes of diseases [1, 2]. The emergence of ultrasound contrast agents (UCAs) is a milestone in the development of ultrasound imaging and offers a tremendous advantage for contrast enhanced ultrasound (CEUS) due to its high contrast and temporal resolution [3,4,5]. Commercial UCAs with diameters of 1–8 μm are typically designed to serve only as blood pool agents, but not for surrounding tissues or cells [6,7,8]. A small particle size bubble is required for ultrasound contrast-enhanced agents.
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