Study on phase transition and contrast-enhanced imaging of ultrasound-responsive nanodroplets with polymer shells

Ultrasound-responsive nanodroplets show great potential in ultrasound diagnosis and targeted tumour therapy due to their unique phase transition properties. However, the mechanism underlying the phase transition and the properties of contrast-enhanced imaging have not been well elucidated, which impedes the development and application of nanodroplets in clinic. Herein, the phase transition of polymeric nanodroplets with a core of perfluoronpentane (PFP) was studied through the measurement of particle size and in vitro/in vivo contrast-enhanced imaging, and imaging performance was further evaluated by introducing intensity analysis of acoustic signals. The average particle size of nanodroplets increased and became polydispersed when heated at 37 °C, which may result from vaporization of a portion of nanodroplets. For imaging in vitro, no acoustic signals were observed at 25 °C when the mechanical index (MI) varied from 0.08 to 1.0. At 37 °C, acoustic signals were observed for MI ≥ 0.4, and the intensity was stronger for higher MIs. For imaging in mice livers, the nanodroplets showed similar contrast enhancement behaviours with SonoVue® at low MI (0.08), which produced strong acoustic signals immediately and were cleared within 10 min. The acoustic signals at high MI (1.0) were weaker but lasted more than 1 h. These results indicated that the phase transition of polymeric nanodroplets could be induced by diagnostic ultrasound, and contrast-enhanced imaging is closely related to particle size, temperature and MI. This study provides a better understanding of phase transition and contrast-enhanced imaging for ultrasound-responsive nanodroplets with polymer shells.