Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging.

Recently, perfluorocarbon (PFC) nanodroplets were introduced as contrast agents for imaging and image-guided therapy. For example, in sonography, high-intensity ultrasound pulses were used to phase-transition liquid perfluorocarbon to produce gas microbubbles. More recently, perfluorocarbon nanodroplets with encapsulated gold nanorods were used as dual ultrasound/photoacoustic contrast agents. To expedite clinical translation, we synthesized and characterized ICG-loaded perfluorocarbon nanodroplets, i.e., constructs comprising biocompatible, nontoxic and biologically safe materials. We then demonstrated enhanced photoacoustic contrast through optically triggered phase transition of PFC nanodroplets and ultrasound contrast from the resulting PFC bubbles. We assessed the quality enhancement of photoacoustic and ultrasound images through analysis of contrast and contrast-to-noise ratio. We further investigated the changes in image contrast due to increased ambient temperature. Our studies suggest that ICG-loaded perfluorocarbon nanodroplets may become a valuable tool for various imaging modalities, and have promising therapeutic applications.