Content of review 1, reviewed on December 09, 2020

Yin et al. present a detailed and well-defined study on the application of nanoscale bubble agents (nanobubbles) for high-quality ultrasonic imaging in particular relation to their extravasation into target tumors. The title reflects the work conducted in the study accurately, with the abstract succinctly outlining the aims and results. Briefly, phospholipid-stabilized nanobubbles were synthesized using a thin-film hydration-sonication method, with their physicochemical properties (size, size distribution, zeta potential) characterized. These nanobubbles were subject to additional various in vitro tests before finally exploring their passive tumor-targeting abilities and ultrasound imaging capabilities in vivo. They found their nanobubbles were able to passively extravasate to tumor sites of interest in mouse models as well as demonstrate contrast-enhancing abilities for high-quality images. The discussion brings forth novel points and a detailed explanation explaining their results and justifying the selection of their experimental design.

The article is very easy to digest and many researchers interested in exploring the usage of phospholipid-stabilized nanobubbles, such as myself, would find this useful. In particular, their experimental design was well described throughout the methodology with an appropriate number of figures demonstrating their in vitro and in vivo results. Not only does this paper show that nanobubbles can be utilized as ultrasonic contrast agents for imaging, but they also show the possibility of being loaded with difficult to load therapeutic cargo (i.e. drugs, genetic material) and passively delivering this payload to tumors.

However, there were certain points (both major and minor) that could be improved upon and are listed below: 1. The methodology, particularly the nanobubble synthesis procedure, could have been included in slightly greater detail in the given abstract. 2. Figures or tables of the acoustic characteristics of the nanobubbles would have been good to include and compare to commercial microbubble contrast agents. 3. The introduction could have emphasized the concerns of nanoscale agents retaining their contrast enhancement properties before diving into the purpose of the study.

Minor points for improvement include: 4. The overall text of the figures could be a bit larger with the marker sizes shrunk as well 5. The x-axis displaying the size distribution of the nanobubbles in Figure 3B could have been spaced a bit better. 6. The usage of dotted and solid colored lines aid visualization but are unnecessary, particularly if only two experimental groups are being compared.


    © 2020 the Reviewer.


    Tinghui, Y., Ping, W., Rongqin, Z., Bowen, Z., Du, C., Xinling, Z., Xintao, S. 2012. Nanobubbles for enhanced ultrasound imaging of tumors. International Journal of Nanomedicine.