Preparation of Phase-Transition Perfluoropentane Nanodroplets Modified by Folate for Ultrasound Molecular Imaging in Ovarian Cancer

Abstract

This study aimed to develop a hybrid platform based on folate-modified phospholipid-shell and perfluoropentane nanodroplets (FA-NDs), which could in vitro and in vivo target ovarian cancerand enhance ultrasound imaging after acoustic droplet vaporization (ADV) induced by low-intensity focused ultrasound (LIFU). The nanodroplet was fabricated with HSPC, DSPE-PEG (2000)-folate, DPPG, cholesterol and perfluoropentane using lipid film hydration method and rotary evaporation method. The nanodroplet stability was evaluated at 4°C and 37 °C respectively. The in vitro targeted efficiency were tested with SKOV3 cells and in vitro ADV was appraised in jellium model with LIFU. The in vivo targeted efficiency and acoustic droplet vaporization were evaluated with SKOV3 tumor-bearing nude mice. The nanodroplets were successfully prepared with good size uniformity (particle size 321±67 nm). The nanoparticles remained stable for 48 h at 4°C and 1 h at 37 °C. In vitro targeted experiments exhibited a perfect binding efficiency of FA-NDs to SKOV3 cells. In vitro ADV profiles displayed obvious ultrasound enhancement in both B-mode and CEUS-mode when LIFU power was elevated to 5 W. In vivo and ex vivo fluorescence imaging displayed that FA-NDs possessed outstanding specificity to targeted solid tumor. Both the qualitative and quantitative results of in vivo ADV in mice tumor nodule manifested that FA-NDs underwent phase transition upon the LIFU exposure. The results demonstrated that the FA-NDs system is a potential platform for targeted conjunction and enhancing ultrasound imaging via ADV using LIFU.