Ultrastable fluorinated copolypeptide nanodroplets of loaded mixed liquids with low vaporization threshold

Abstract

The expansion of ultrasound molecular imaging applications warrants a reduction in ultrasound contrast agent size and significant advancement in the in vivo stability of shell-stabilized bubbles. The shift from first to second-generation ultrasound contrast agents was marked by an improvement in stability as air was replaced by hydrophobic gases like perfluoropropane and sulfur hexafluoride. Further enhancements may be facilitated by focusing on strategies to retain the encapsulated gas within the ultrasound contrast agent shell despite extreme mechanical deformations. In this study, we developed a novel ultrasound contrast agent with a unique shell structure and a specially-formulated, low-boiling fluorinated liquid interior, resulting in superior stability during repeated and prolonged ultrasound-induced oscillations. Our ultra-stable nanodroplets can withstand sustained in vitro ultrasound exposure with minimal signal attenuation and can induce significant signal enhancement and delay in signal attenuation in the kidney, liver, and tumor tissues during in vivo experiments. Furthermore, encapsulating photosensitizers within these nanodroplets and leveraging photothermal effects could further augment the ultrasound imaging signal and verify its efficacy in tumor therapy. The creation of highly stable nanodroplets opens immense potential to augment the role of ultrasound in molecular imaging, therapy, and drug delivery.