Theragnostic Nanodroplets for Photoacoustic and Ultrasound Signal Amplification and Optically Triggered Vaporization-Induced Drug Release

Theragnostic contrast agents are among the newest tools for simultaneous diagnosis and therapy, but still have limitations in terms of their contrast enhancement capabilities and, consequently, their effectiveness. Among the various biomedical imaging modalities, photoacoustic (PA) imaging is a technology that can enhance diagnostic capacity by use of contrast agents; however, the traditional mechanism for generating PA signals by inducing thermal expansion is limited by low efficiency and sensitivity. To address these issues, we have developed an Indocyanine Green (ICG)-loaded perfluoropentane (Pen) nanodroplet for vaporization-induced amplification of PA signals, and enhancement of ultrasound echogenicity by a vaporization mechanism. We found that vaporization was a more effective mechanism for signal enhancement than thermal expansion. Under laser irradiation, vaporization of ICG nanodroplets encapsulating perfluoropentane by a graded temperature increase enabled the visualization of a PA image. The gas phase of perfluoropentane present after evaporation-induced acoustic impedance mismatch relative to the surroundings, causing echogenic signals to be effectively propagated for ultrasonographic detection. The nanodroplet also demonstrated therapeutic efficacy through optically triggered release of paclitaxel via vaporization, which reduced the viability of breast cancer cells. These findings suggest that the ICG-Pen nanodroplet is a promising theragnostic contrast agent that can both amplify photoacoustic and echogenic signals and target local delivery of chemotherapeutic drugs in cancer treatment.